The burden of trachoma in the rural Nile Delta of Egypt: a survey of Menofiya governorate.

BACKGROUND: Evidence of widespread distribution of trachoma in Egypt had not been clarified as previous surveys were limited to individual communities which may not have been representative of the general population. The Nile Delta of Egypt presents a unique environment for trachoma to persist. Economic improvements in the past decade have affected even the poorest rural environments; availability of electricity is now found in many rural communities. Availability of water in Nile Delta has always been good but poor hygienic conditions have been the primary factor in trachoma transmission. A survey of trachoma was undertaken in Menofiya governorate to determine if Egypt should be identified as trachoma endemic and targeted for trachoma control efforts. METHODS: A multistage random cluster study design was used with the target population defined as adults aged 50 and over and children aged 2-6 years from throughout the governorate. Among preschool children only trachoma was graded while among adults presenting visual acuity and cause of vision loss or blindness were also recorded. Adults were interviewed regarding past trichiasis surgery; those currently with trichiasis or a history of trichiasis surgery were also interviewed regarding outcome of surgery. RESULTS: A total of 3272 children aged 2-6 and 3322 adults age 50+ were enumerated. Among the children 81.3% were examined and among the adults 73.0% were examined. Active trachoma (follicles (TF) and/or intense inflammation (TI)) was found among 36.5% (95% confidence interval (CI) 34.7-38.3%) of the children. TI was 1.89 (95% CI 1.22-2.94) times more common in rural children compared to urban children. The prevalence of trichiasis (TT) in adults was 6.5%; women had an age adjusted odds of trichiasis of 1.68 (95% CI 1.18-2.39) compared to men. Trichiasis was 2.11 times (95% CI 1.33-3.37) more common in rural Menofiya compared to urban Menofiya. TT accounts for blindness (presenting vision <3/60) in 8% of patients and accounts for 13.2% of visual impairment. Overall, trichiasis surgical coverage was 34.4%, slightly higher among men than women. The outcome of trichiasis surgery was poor in 44.4% of cases. CONCLUSION: Trachoma is a serious public health problem in Menofiya governorate and a significant contributor to vision loss. These findings would suggest that continued poor hygienic conditions in rural Egypt have limited the reduction of active trachoma even in the face of significant improvements in socioeconomic status. Furthermore, the high proportion of trichiasis surgery cases with a poor outcome would indicate a need to reassess current surgical practices in Egypt and improve training and monitoring.

Hyperhomocysteinemia is related to residual glomerular filtration and folate, but not to methylenetetrahydrofolate-reductase and methionine synthase polymorphisms, in supplemented end-stage renal disease patients undergoing hemodialysis.

Glomerular filtration is one of the major determinants of plasma total homocysteine (tHcy). To evaluate the respective roles of residual glomerular filtration (by measuring a specific protein marker, cystatin C), genetic polymorphisms and nutritional status in tHcy blood levels in end-stage renal disease patients (ESRD) under hemodialysis and supplemented with folate, we measured tHcy, folate, vitamin B12 (B12), creatinine, cystatin C, albumin and C-reactive protein and determined the polymorphism of methylenetetrahydrofolate reductase (MTHFR) (C677T and A1289C) and of methionine synthase (MS) (A2756G) in 114 ESRD patients before hemodialysis and 76 control subjects. All patients received a folate supplementation of 700 microg/day. Hyperhomocysteinemia was observed in all patients and exceeded the upper normal limit by 2-fold in 52.4% of the patients. Serum folate was significantly increased and the B12 level was not different from controls. Folate, Cystatin C and creatinine were significantly correlated to tHcy, while no correlation was found between tHcy, albumin and C-reactive protein. No difference in genotype frequency between ESRD patients and controls was found for MTHFR A1289C and MS A2756G. The MTHFR 677TT genotype was less frequent and was associated with a significantly higher tHcy level in patients. Folate and residual glomerular filtration estimated by cystatin C and creatinine levels were two independent determinants of tHcy in ESRD patients. These data suggest that hyperhomocysteinemia is a consequence as well as a complicating factor of renal failure.

Hepatitis C virus infection in a community in the Nile Delta: risk factors for seropositivity.

The purpose of this study was to identify risk factors for hepatitis C virus (HCV) infection in a rural village in the Nile Delta with a high prevalence of antibodies to HCV (anti-HCV). One half of the village households were systematically selected, tested for anti-HCV, and interviewed: 973 of 3,999 (24.3%) subjects were anti-HCV-positive (reflecting prior HCV infection but not necessarily current liver disease), with nearly equal prevalence among males and females. Anti-HCV prevalence increased sharply with age among both males and females, from 9.3% in those 20 years of age and younger to >50% in those older than 35, suggesting a cohort effect with reduced transmission in recent years. Multivariate regression was used to estimate independent effects of risk factors on seropositivity. Among those over 20 years of age, the following risk factors were significantly associated with seropositivity: age (P <.001); male gender (odds ratio [OR] = 2.5, 95% CI = 1.3-4.7); marriage (OR = 4.1, 2.4-6.9); anti-schistosomiasis injection treatment (OR = 2.0, 1.3-2.9); blood transfusion (OR = 1.8, 1.1-2.9), invasive medical procedure (surgery, catheterization, endoscopy, and/or dialysis) (OR = 1.5, 1.1-1.9); receipt of injections from "informal" health care provider (OR = 1.3, 1.0-1.6); and cesarean section or abortion (OR = 1.4, 1.0-1.9). Exposures not significantly related to anti-HCV positivity in adults included: history of, or active infection with, Schistosoma mansoni, sutures or abscess drainage, goza smoking in a group, and shaving by community barbers. Among those 20 years old or younger, no risk factors were clearly associated with anti-HCV positivity; however, circumcision for boys by informal health care providers was marginally associated with anti-HCV (OR = 1.7, 1.0-3.0). Prevention programs focused primarily on culturally influenced risks in rural Egyptian communities are being implemented and evaluated.

Hepatitis C virus (HCV) infection in a community in the Nile Delta: population description and HCV prevalence.

This report describes a cross-sectional survey of the prevalence of antibodies to hepatitis C virus (anti-HCV) in a rural Egyptian community in the Nile Delta. One half of the village households were systematically selected and examined by questionnaire and testing sera for anti-HCV and HCV RNA. Blood samples were obtained from 3, 888 (75.4%) of 5,156 residents >/=5 years of age; an additional 111 samples were obtained from children younger than 5 years. Overall, 973 (24.3%) of 3,999 residents were anti-HCV-positive, and the age- and gender-adjusted seroprevalence was 23.7%. Anti-HCV prevalence increased sharply with age, from 9.3% in those 20 years of age and younger to >50% in those older than 35 years. Currently or previously married individuals were more likely to be seropositive than those never married, controlling for age (Mantel-Haenszel risk ratio = 1.8; 95% CI: 1.3, 2.6). Of the 905 anti-HCV-positive samples tested, 65% were also positive for HCV RNA. Active schistosomal infection was not associated with anti-HCV status; however, history of antischistosomal injection therapy (reported by 19% of anti-HCV positives) was a risk for anti-HCV (age-adjusted risk ratio = 1.3; 95% CI: 1.2, 1.5). This study, the largest community-based survey to date, supports earlier reports of high levels of anti-HCV among adults in rural areas of Egypt, although many of those who are seropositive will not have active liver disease. The large reservoir of HCV infection in the community provides an opportunity to investigate risk factors for transmission, the natural history of infection and effectiveness of preventive methodologies, and raises concern about the prospect of an increasing incidence of chronic liver disease in the coming decades.

The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt.

BACKGROUND: The population of Egypt has a heavy burden of liver disease, mostly due to chronic infection with hepatitis C virus (HCV). Overall prevalence of antibody to HCV in the general population is around 15-20%. The risk factor for HCV transmission that specifically sets Egypt apart from other countries is a personal history of parenteral antischistosomal therapy (PAT). A review of the Egyptian PAT mass-treatment campaigns, discontinued only in the 1980s, show a very high potential for transmission of blood-borne pathogens. We examine the relative importance of PAT in the spread of HCV in Egypt. METHODS: The degree of exposure to PAT by cohort was estimated from 1961-86 Ministry of Health data. A cohort-specific exposure index for PAT was calculated and compared with cohort-specific HCV prevalence rates in four regions. FINDINGS: HCV prevalence was calculated for 8499 Egyptians aged 10-50 years. A significant association between seroprevalence of antibodies to HCV and the exposure index (1.31 [95% CI 1.08-1.59]; p=0.007) was identified across four different regions. In all regions cohort-specific HCV prevalence was lowest in children and young adults than in older cohorts. These lower prevalence rates coincided with the gradual and final replacement of PAT with oral antischistosomal drugs at different points in time in the four regions. INTERPRETATION: The data suggest that PAT had a major role in the spread of HCV throughout Egypt. This intensive transmission established a large reservoir of chronic HCV infection, responsible for the high prevalence of HCV infection and current high rates of transmission. Egypt's mass campaigns of PAT may represent the world's largest iatrogenic transmission of blood-borne pathogens.

Hepatitis C in a community in Upper Egypt: I. Cross-sectional survey.

The prevalence of antibody to hepatitis C virus (anti-HCV) was determined in a cross-sectional survey in a village in Upper Egypt. Exposure and demographic characteristics were obtained through a questionnaire. Antibody to hepatitis C virus was assessed using a second generation enzyme immunoassay, and the presence of HCV RNA was tested using a reverse transcriptase-polymerase chain reaction. Collection of blood samples was targeted at those > or = 5 years old, and obtained from 62.8%. This report describes the community, the HCV infection characteristics of the subjects, and evaluates some factors associated with presence of anti-HCV. Of the 6,031 participants, 522 (8.7%) were anti-HCV positive. Prevalence was higher among males than females (11.3% versus 6.5%; P < 0.001). It was greater among those > 30 years of age than among those < or = 30 years of age (20.0% versus 3.6%; P < 0.001). Those who were less educated, farmed, provided health care, and were currently married had a significantly higher anti-HCV prevalence than those who were not; however, these associations were not significant after adjusting for age. Although active infections with Schistosoma haematobium were not associated with anti-HCV, a history of past infection was (age-adjusted risk ratio [RR] = 2.1, 95% confidence interval [CI] = 1.8, 2.4); 134 persons who had a history of receiving parenteral anti-schistosomal therapy had a higher age-adjusted RR (3.0; 95% CI = 2.5, 3.7) for anti-HCV than those who did not. Hepatitis C virus RNA was detected in 62.8% of the anti-HCV positive subjects, without significant variation by age, gender, education, or marital status. The prevalence of anti-HCV in Upper Egypt is high, albeit lower than in Lower Egypt, with continuing but limited transmission indicated by the lower prevalence in residents < or = 30 years old.

GSTM1 and GSTT1 genes are potential risk modifiers for bladder cancer.

The role of the polymorphic glutathione S-transferase genes GSTM1 and GSTT1 in the development and in the clinicopathological outcome of bladder cancer was investigated in 37 Egyptian bladder cancer patients and 34 matched controls. Of the 37 patients studied, 26 had transitional cell carcinoma (TCC) and 11 had squamous cell carcinoma (SCC). Fourteen out of twenty-six TCC and four out of eleven SCC patients were infected with schistosoma. We observed an increased relative risk for bladder cancer associated with the GSTM1 null genotype (OR = 2.99; 95% CL = 1.01-9.00; p = 0.02). The relative risk was more pronounced in squamous cell carcinoma (SCC) (OR = 5.70; 95% CL = 0.91-36.70; p = 0.03) than in transitional cell carcinoma (TCC) (OR = 2.39; 95% CL = 0.73-7.90; p = 0.08). Our results also indicate that the GSTT1 polymorphism is individually associated with increased risk for bladder cancer (OR = 4.93; 95% CL = 1.39-18.42; p = 0.004) with no preferential increase in risk with respect to the type of the carcinoma. Individuals with the null genotype for both GSTM1 and GSTT1 were at a significantly higher risk for developing bladder cancer than individuals with both genes present (OR = 9.92; 95% CL = 1.84-46.90; p = 0.001). These individuals were more susceptible to developing SCC than TCC (OR = 14.16; 95% CL = 1.35-131.35; p = 0.01; and OR = 8.5; 95% CL = 1.38-60.10; p = 0.007, respectively). In conclusion, our results indicate that the null genotypes for GSTM1 and GSTT1, either individually or in combination, are important host risk factors for bladder cancer. In addition, the null GSTM1 genotype may also affect the clinicopathological tumor outcome. Since the deleted genotypes for GSTM1 and GSTT1 are prevalent in the general population, the identification of these individuals may provide a useful public health approach for early detection and prevention of environmental cancers.

Biomarkers of human exposure to pesticides.

For centuries, several hundred pesticides have been used to control insects. These pesticides differ greatly in their mode of action, uptake by the body, metabolism, elimination from the body, and toxicity to humans. Potential exposure from the environment can be estimated by environmental monitoring. Actual exposure (uptake) is measured by the biological monitoring of human tissues and body fluids. Biomarkers are used to detect the effects of pesticides before adverse clinical health effects occur. Pesticides and their metabolites are measured in biological samples, serum, fat, urine, blood, or breast milk by the usual analytical techniques. Biochemical responses to environmental chemicals provide a measure of toxic effect. A widely used biochemical biomarker, cholinesterase depression, measures exposure to organophosphorus insecticides. Techniques that measure DNA damage (e.g., detection of DNA adducts) provide a powerful tool in measuring environmental effects. Adducts to hemoglobin have been detected with several pesticides. Determination of chromosomal aberration rates in cultured lymphocytes is an established method of monitoring populations occupationally or environmentally exposed to known or suspected mutagenic-carcinogenic agents. There are several studies on the cytogenetic effects of work with pesticide formulations. The majority of these studies report increases in the frequency of chromosomal aberrations and/or sister chromatid exchanges among the exposed workers. Biomarkers will have a major impact on the study of environmental risk factors. The basic aim of scientists exploring these issues is to determine the nature and consequences of genetic change or variation, with the ultimate purpose of predicting or preventing disease.

The CYP2D6 extensive metabolizer genotype is associated with increased risk for bladder cancer.

Inheritance of certain polymorphic metabolizing genes is associated with the development of a number of environmental cancers and may also influence the clinicopathological tumor outcome. We have investigated the association between the inheritance of the polymorphic cytochrome P-450 2D6 (CYP2D6) gene and the development of transitional and squamous cell carcinomas (TCC and SCC) of the bladder in 37 Egyptian cancer patients and 27 matched controls. Genotypic analysis using the polymerase chain reaction (PCR) and the restriction fragment length polymorphism (RFLP) assays revealed that the CYP2D6 extensive metabolizer genotype (CYP2D6*1A) is over represented in bladder cancer patients compared to controls (79 versus 44%, respectively) and is significantly associated with increased risk for bladder cancer (odds ratio (OR) = 4.5, 95% confidence limit (CL) = 1.3-15.7, P = 0.006). Our results also indicate that individuals who have inherited this genotype are more likely to develop TCC (OR = 5.9, 95% CL = 1.4-27.9, P = 0.006) rather than SCC (OR = 3.1, 95% CL = 0.7-15.9; P = 0.09). When the relative risk associated with this genotype was estimated among subjects who were smokers or schistosoma infected, the same tendency towards the development of TCC was observed. These data suggest that the predisposing CYP2D6 gene may not only increase the risk for bladder cancer among Egyptians, but may also influence the clinicopathological tumor outcome.

A multiplex PCR procedure for polymorphic analysis of GSTM1 and GSTT1 genes in population studies.

A deletion polymorphism in glutathione S-transferase theta (GSTT1) gene was recently discovered in humans. Similar to the GSTM1 gene, GSTT1 is also recognized as a risk modifier in exposed populations. To evaluate the role of genetic polymorphism in health effects, the combined genetic polymorphism of different genes should be taken into consideration. In the present study, we have developed a multiplex PCR approach for simultaneous replication of both genes for molecular analysis. The multiplex PCR protocol was validated using donor DNA with different polymorphic combinations for both genes from two different ethnic populations (North Americans and Egyptians). The prevalence of the GSTM1 null genotype was 51% among North Americans and 44% among Egyptians. The prevalence of the GSTT1 null genotype was 15% among North Americans and 14.7% among Egyptians. Combined polymorphism analysis of both genes revealed that 6.3% of North Americans harbor the deleted genotype of both genes compared to 8.8% of the Egyptians. The data indicate that there is no major difference in allelic distribution of both genes between the ethnic populations. The multiplex PCR assay used in this study has the advantage of reducing the time, effort and cost required to carry out such analysis. It will also significantly enhance the ability to use genetic screening techniques as a potential tool for early detection of health outcomes in exposed populations.

Genetic polymorphism of GSTM1, CYP2E1 and CYP2D6 in Egyptian bladder cancer patients.

Polymorphic changes in the GSTM1, CYP2E1 and the CYP2D6 genes have been reported to be individually associated with increased susceptibility to certain cancers. In the present study, the relationship between genetic polymorphism for these genes and development of urinary bladder cancer among Egyptian patients was investigated. Our results indicate that the frequency of bladder cancer patients with the GSTM1 null genotype is significantly higher than that of the normal controls (86.3 and 47.6%, respectively) with an odds ratio (OR) of 6.97 (95% CL -1.59-30.57, Fisher's exact P = 0.008). In contrast, our investigation failed to demonstrate any difference in the distribution of CYP2E1 polymorphism between bladder cancer patients and controls as detected by PstI restriction fragment length polymorphism (RFLP) analysis. RFLP analysis of the CYP2D6 gene revealed a non-significant increase in the number of extensive metabolizers (EM) among the patients compared to the controls (68 versus 48%). However, the EM genotypes enhances the risk further for individuals harboring the GSTM1 null genotype as individuals harboring both the EM and the GSTM1 null genotypes have an odds ratio of 14.0 (95% CL = 1.3- 151.4, Fisher's exact P = 0.02) compared to individuals harboring the EM and the GSTM1 +/+ genotypes. In conclusion, our results indicate that genetic polymorphism, especially in GSTM1 and CYP2D6 could play an important role as host risk factors for development of urinary bladder cancer among Egyptians.

Chromosomal aberrations and micronuclei in reinforced plastics workers exposed to styrene.

The aim of this study was to investigate the cytogenetic changes induced in humans exposed to styrene in a reinforced plastics plant. Blood and urine samples were collected from 18 styrene exposed workers and 18 age and sex matched control subjects from the administrative department of the same factory. Chromosome aberrations (CAs) and micronuclei (MN) (cytokinesis block method) were analyzed in blood lymphocytes. All of the subjects included in the study were male non-smokers. The duration of employment ranged from 10 to 22 years (14.3 +/- 4.4). In order to monitor exposure to styrene, urinary mandelic acid (MA) levels were measured using a standard colorimetric method. The level of thioethers in the urine was also determined colorimetrically. The mean level of mandelic acid was significantly higher in the exposed workers (328.44 +/- 266.21 mg/g creatinine) compared with that of the controls (50.09 +/- 16.84 mg/g creatinine) (p < 0.05). The level of urinary thioethers was found to be higher among the exposed workers. The number of cells with chromosomal aberrations was significantly higher in the workers (6.06 +/- 4.41) compared with the controls (3.44 +/- 2.28) (p < 0.05). There was no significant increase in the frequency of micronuclei in the exposed workers compared to controls. Our results support earlier findings on increased rates of chromosomal aberrations in reinforced plastics workers.

Monitoring of human populations at risk by different cytogenetic end points.

Humans are exposed to a large number of environmental genotoxic agents. These can increase the probability that somatic mutation will occur. The use of genotoxicity testing is essential for assessment of potential human toxicity so that hazards can be prevented. Cytogenetic monitoring of human populations exposed to chemicals has proved to be a useful tool for detecting the chemical mutagenic effects. Cytogenetic analysis of human chromosomes in peripheral lymphocytes allows direct detection of mutation in somatic cells. Cytogenetic monitoring of a group of traffic policemen from Cairo, Egypt, was an example of a human population study. The induction of chromosomal damage was studied in a group of 28 traffic policemen with exposure of over 10 years and a control group of 15 policemen trainers. Blood lead level was significantly higher in the traffic policemen (30 +/- 8.7) unit compared to the control group (18.2 +/- 1.2) unit. The percentage of chromosomal aberrations (7.7 +/- 3.1), as well as the mean sister chromatid exchanges (7.5 +/- 3.4), were significantly higher among the traffic policemen than in the control group. The percentage of chromosomal aberrations was 2.8 +/- 2.1 and the mean sister chromatid exchanges was 4.8 +/- 2.9 in the control group. On the other hand, the increase in chromosome damage among the traffic policemen was enhanced further by smoking. Several problems that are found in biomonitoring studies are discussed.

Assessment of cytogenetic changes in human populations at risk in Egypt.

Humans are exposed to numerous environmental agents that can increase the probability of mutagenicity and carcinogenicity. Most of environmental exposures involve concurrent or sequential exposure to several agents in air, water, and food. Interactive effects in carcinogenesis have been described for a certain number of combinations of agents. They are described in terms of enhancement or inhibition of carcinogenesis. Risk assessment of exposure to environmental agents can start either from laboratory studies after exposure to different agents or from epidemiological studies in relation to actual exposure. The use of genotoxicity testing is essential for assessment of potential human toxicity so that hazards can be prevented. Cytogenetic monitoring of human populations exposed to environmental agents has proved to be a useful tool for detecting their mutagenic effects. Cytogenetic analysis of human chromosomes in peripheral lymphocytes allows direct detection of mutation in somatic cells. Various methods can be used for chromosomal analysis (conventional chromosomal analysis, sister chromatid exchange, micronucleus frequency detection). Micronucleus frequency can be detected either in peripheral blood lymphocytes or in exfoliated cells. Different examples of human population studies are presented in this review. Several problems which are found in biomonitoring studies are discussed.

Chromosomal aberrations and micronucleus frequency in nurses occupationally exposed to cytotoxic drugs.

In this study, we evaluated the effect of low level occupational exposure of nurses in a medical oncology unit in Cairo, Egypt, to anticancer drugs. Twenty nurses who constantly handled these drugs and 20 controls, matched according to age and sex, were examined. Metaphase chromosomes were studied. Percentages of metaphases with chromosomal aberrations were significantly higher (P < 0.001) in the exposed group (6.1 +/- 2.7) versus the controls (2.6 +/- 1.6). The detected chromosomal aberrations were in the form of chromatid gaps, chromatid breaks and acentric fragments. Micronucleated peripheral blood lymphocytes were also analyzed in cytochalasin B treated binucleated lymphocytes. There was significant increase in cells with micronuclei (P < 0.001) in nurses (10.05 +/- 4.71) in comparison to the matched control (5.42 +/- 2.22) (P < 0.001). Nurses exposed to the cytotoxic drugs for > or = 48 months showed a slightly higher frequency of cells with chromosomal aberrations as well as micronucleated cells than those exposed for < 48 months, but these differences were not statistically significant (P > 0.05).

Micronuclei, chromosomal aberrations and aflatoxin-albumin adducts in experimental animals after exposure to aflatoxin B1.

Rats and mice differ markedly in sensitivity to aflatoxin B1 (AFB1) hepatocarcinogenicity, the former being sensitive and the latter resistant. Animals were treated with single doses of different concentrations of AFB1, between 0.01 and 1.0 microgram AFB1/g body weight. The frequency of chromosomal aberrations and micronuclei in the bone marrow was measured and compared to the level of AFB1 bound covalently to albumin in the peripheral blood. Both chromosomal aberrations and micronuclei were significantly increased in treated rats compared to the control group at doses above 0.1 microgram/g. In contrast, in mice, a slight increase in chromosome aberrations was seen in the highest dose group (1.0 microgram/g) but no increase in micronuclei was observed at any of the doses. The level of chromosomal aberrations was about 10 times higher in rats than in mice at the highest dose of AFB1. AFB1-albumin (AF-alb) adducts did not show a strong dose-response increase after treatment in mice, whereas in rats the levels increased linearly with dose of AFB1 and there were strong correlations at the individual rat level with both chromosomal aberrations (r = 0.92; p < 0.0001) and micronucleus frequency (r = 0.86; p < 0.0001). These data suggest that the AF-alb may reflect the level of genetic alteration resulting from the initial binding of this carcinogen to cellular DNA. Therefore, this adduct used as a biomarker in studies of human exposure to aflatoxin may provide information not only on exposure but also on the risk of genetic alterations consequent to that exposure.

Localized induction of micronuclei in the oral mucosa of xeroderma pigmentosum patients.

Xeroderma pigmentosum (XP) patients are predisposed not only to skin cancers but also to tumors on the tip of the tongue. Although this enhanced risk has been attributed to a defect in the repair of DNA damage induced by ultraviolet rays from sunlight there is a lack of data showing that DNA damage is occurring in vivo at these sites. In order to determine whether a relationship exists between exposure to ultraviolet light and the level of chromosomal breakage occurring in epithelial tissue in XP patients, the exfoliated cell micronucleus test was applied to different sites in the oral cavities of four XP patients: the right and left buccal mucosa, the dorsal tip of the tongue and the palate. Six Egyptian controls were sampled concurrently. Micronucleus (MN) frequencies were higher in XP patients than in controls for all sites except the palate, where technical difficulties were encountered. In addition, an unequal distribution of the frequency of micronucleated cells was found in the different sample sites of the oral cavity in the XP patients, with the greatest elevation in frequencies among cells collected from the dorsal tip of the tongue. In contrast, the frequency of micronucleated cells did not vary significantly in samples from different sites obtained from the controls. These data suggest that the complex interplay of host and environmental factors can affect MN frequencies when this endpoint is used to quantify in vivo genotoxic damage in a tissue.

Inflammation, chromosomal instability, and cancer: the schistosomiasis model.

Evidence is accumulating in support of a role for reactive oxygen species in the etiology of cancer. Inflammatory cells, such as neutrophils, macrophages, and eosinophils, are an important endogenous source of oxygen radicals. Stimulation of these cells by tumor promoters or by foreign bodies (parasites, bacteria, etc.) causes the release of reactive oxygen species. Laboratory studies have shown that genetic damage and neoplastic transformation are induced in vitro in cells cocultured with activated inflammatory cells. We have recently begun to study the role of inflammatory reactions in inducing genetic damage in a human population. This paper describes our initial studies of Egyptian patients infected with Schistosoma haematobium. This infection induces chronic inflammation and irritation in the urinary bladder and is associated with increased cancer at this site. We describe a recently completed population study that shows that infected individuals have elevated levels of genetic damage in their bladders, as measured by the exfoliated cell micronucleus test. Treatment that kills the parasite also reduces the micronucleus frequencies. We also explore the hypothesis that altered sensitivity of clones of cells in these patients to reactive oxygen species could be a force that drives the development of neoplasia by facilitating clonal expansion. Evidence is presented for the possible involvement of loci on chromosome 11 in controlling the level of chromosomal breakage caused by oxidative damage. We have shown that bladder carcinoma cells are sensitive to micronucleus induction by promoter-activated neutrophils and that they can be protected from this damage by insertion of a normal chromosome 11. Further work is in progress to define the source of chromosomal breakage in schistosomiasis patients and to begin to develop an understanding of the host factors protecting bladder cells in these individuals from genetic damage.

Praziquantel (antischistosomal drug): is it clastogenic, co-clastogenic or anticlastogenic?

Schistosoma haematobium infection is the most common health problem in Egypt. It is strongly associated with the development of urinary bladder carcinoma. The actual cause for the development of cancer is still under investigations, it can be due to mechanical irritation from schistosomiasis ova, the infection itself or the drugs which are used to treat the patients. Praziquantel (PQ) is a commonly used drug to treat schistosomiasis patients. In mice, an in vivo cytogenetic study showed that PQ is not clastogenic in mice. The frequency of micronuclei in all the study groups were insignificantly different from the control group (p > 0.05). However, it enhanced the clastogenicity of benzene at a very high dose. Results from combined exposure with benzene and PQ showed a significant PQ dose-dependent increase in micronucleus frequency (p < 0.05). A metabolite study revealed that PQ enhanced the metabolism of benzene to form muconaldehyde which may be responsible for the enhancement effect. In schistosomiasis patients, two cytogenetic studies were carried out before and after treatment with PQ. In one of these studies, peripheral blood lymphocytes were examined from schistosomiasis patients to detect chromosomal aberrations (CAs) and micronuclei (MN) before and after treatment with PQ. There was no significant increase in CAs in patients compared with the controls (p > 0.05). The frequency of MN was significantly higher in the infected persons (0.59 +/- 0.44) than the control individuals (0.23 +/- 0.23) (p < 0.05). After treatment, there was no significant change in both parameters. The other study was conducted to determine whether infection with this parasite resulted in an increase of chromosomal breakage, micronuclei, in exfoliated urothelial cells. Micronucleus frequencies were significantly higher in the infected group (mean frequency, 0.84 +/- 0.69%) than among controls (mean frequency, 0.12 +/- 0.21%, p < 0.001). Micronucleus frequencies were higher in infected individuals who smoked compared with those who were non-smokers, although this effect was not significant (p > 0.05). The mean micronucleus frequencies were reduced significantly in the group of patients who were followed up (before treatment, 0.80 +/- 0.70%, after treatment, 0.19 +/- 0.23%, p < 0.001), thus supporting a direct involvement of the infection in increased chromosomal breakage in the urothelium and provide proof of the role of PQ in decreasing the risk of cancer development. At this stage, we still need to study the cytogenetic effect of human exposure to environmental agents such as pesticides, smoking, etc., together with treatment with PQ.