Retrospective case-series analysis of haematological malignancies in goldmining areas of South Africa.

BACKGROUND: South Africa (SA)'s high levels of environmental contamination of mine tailings from uranium and its decay products, coupled with remarkably short distances between mine tailings and residential areas, raise concern about whether there is an association between environmental uranium exposure and risk of cancer, including haematological malignancies. OBJECTIVES: We reviewed information on cases from the central hospital offering cancer diagnostics and treatment in a major mining area of SA to describe their basic clinical and demographic characteristics, as part of assessing whether a cancer epidemiological study in this area would be feasible. METHODS: Basic clinical, demographic and residential information on patients with haematological malignancy diagnosed between 2004 and 2013 was collected retrospectively from the patient files at Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg. RESULTS: In total, 1 880 patients aged 18 - 94 years were identified. Referral from distant provinces was not uncommon, but >80% lived within 50 km of the hospital. Non-Hodgkin's lymphoma accounted for 44% of the haematological malignancies, followed by leukaemia with 26%. HIV status was known for 93% of the patients, of whom 47% were HIV-positive. CONCLUSIONS: Caution is required when interpreting spatial distributions of patients, given inaccuracies in residential addresses and referral patterns to the hospital, and with HIV and other infections probable important confounders. Our study therefore shows that active case recruitment is required for accurate assessment of residential information. However, some findings on spatial distributions in the study warrant the continuation of efforts to develop a study protocol to investigate the possible link between uranium exposure in mining areas and haematological malignancies in residents. Disproportionately high incidence rates of haematological malignancies observed in specific districts would be relevant for further investigation.

Retrospective case-series analysis of haematological malignancies in goldmining areas of South Africa

Background. South Africa (SA)'s high levels of environmental contamination of mine tailings from uranium and its decay products, coupled with remarkably short distances between mine tailings and residential areas, raise concern about whether there is an association between environmental uranium exposure and risk of cancer, including haematological malignancies. Objectives. We reviewed information on cases from the central hospital offering cancer diagnostics and treatment in a major mining area of SA to describe their basic clinical and demographic characteristics, as part of assessing whether a cancer epidemiological study in this area would be feasible.Methods. Basic clinical, demographic and residential information on patients with haematological malignancy diagnosed between 2004 and 2013 was collected retrospectively from the patient files at Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg.Results. In total, 1 880 patients aged 18 - 94 years were identified. Referral from distant provinces was not uncommon, but >80% lived within 50 km of the hospital. Non-Hodgkin's lymphoma accounted for 44% of the haematological malignancies, followed by leukaemia with 26%. HIV status was known for 93% of the patients, of whom 47% were HIV-positive.Conclusions. Caution is required when interpreting spatial distributions of patients, given inaccuracies in residential addresses and referral patterns to the hospital, and with HIV and other infections probable important confounders. Our study therefore shows that active case recruitment is required for accurate assessment of residential information. However, some findings on spatial distributions in the study warrant the continuation of efforts to develop a study protocol to investigate the possible link between uranium exposure in mining areas and haematological malignancies in residents. Disproportionately high incidence rates of haematological malignancies observed in specific districts would be relevant for further investigation

Mutagenic activity of the leachate of municipal solid waste landfill.

Organic concentrates were recovered using XAD-2/8 resin adsorption from the leachates of municipal solid waste landfills and their mutagenic activities were tested for 8 months using the Ames Salmonella/microsome assay. Highly polluted leachates (COD and BOD > or = 40 mg/l) generally had equal or higher mutagenic activities than lightly polluted leachates (COD and BOD < 40 mg/l). But there was no clear difference in mutagenicity per amount of concentrate between the two leachates. These results suggest that the mutagenic activity of landfill leachate is decided to some degree by the organic concentration in the leachate. The mutagenic activities detected even in lightly polluted leachates were not so low as those of various kind of surface waters ever reported. It is suggested that it is important to investigate the mutagenic activity of the leachate for evaluation of the impact of landfill leachate on the environment.

Metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline in the male rat.

The metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was studied in the male rat using the radiochemical labels 14C and 3H at positions 2 and 5 of the molecule, respectively. Adult male Fischer 344 rats were administered [2-14C]IQ or [5-3H]IQ by oral gavage at dose levels of 20 or 40 mg/kg body weight. Rats were also given [2-14C]IQ in the diet at a dose level of 300 ppm for 2 days and after administration of unlabelled IQ (300 ppm) in the diet for approximately 6.5 wk for an additional 2 days. In the initial 48 hr following oral administration of 20 or 40 mg [2-14C]IQ/kg body weight, about 40-50% radioactivity was recovered in the urine, and about 30-38% radioactivity was recovered in the faeces. In the initial 72 hr following consumption of [2-14C]IQ (300 ppm) in the diet about 26% radioactivity was recovered in the urine and about 61% radioactivity was recovered in the faeces. Following cannulation of the bile ducts, rats administered a single dose of [2-14C]IQ (40 mg/kg body weight) by oral gavage excreted about 15% of the administered dose in the bile over a period of 2 days. Urine from rats given [2-14C]IQ contained three main polar metabolites that included a glucuronide, a sulphate ester and IQ sulphamate, and a number of less polar metabolites that included IQ, 2-acetylamino-3-methylimidazo[4,5-f]quinoline, 2-aminoimidazo[4,5-f]quinoline and 2-amino-3,6-dihydro-3-methyl-7H-imidazo[4,5-f]quinoline-7-one (7-OH-IQ). Administration of [2-14C]IQ by oral gavage or in the diet gave the same metabolites, but in different amounts. In the faeces of rats given [2-14C] by oral gavage, IQ-sulphamate was the major metabolite in the polar fraction. Non-polar metabolites similar to those found in the urine were also present, but in different amounts. A major, non-polar faecal metabolite, 7-OH-IQ was probably formed as a result of the activity of the intestinal bacterial flora. In rats given a single gavage dose of [2-14C]IQ, excretion of metabolites was higher in the urine and lower in the faeces compared with that in animals fed [2-14C]IQ in the diet. One polar metabolite present in the urine, IQ-sulphamate (39%), was found at considerably higher levels in rats dosed orally with IQ compared with those fed IQ (less than 6%). Thus, IQ is extensively metabolized to give a number of polar and non-polar metabolites, the amounts of which depend, in part, on the mode of dosing.

A comparison of the carcinogenicity of N-nitrosodiethylamine and N-nitrosodimethylamine after intratracheal instillation into Syrian golden hamsters.

N-Nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) were instilled intratracheally into male Syrian golden hamsters once a week for 15 wk. The total dosages were 1.5 mg and 7.5 mg of NDEA and 0.75 mg and 1.5 mg of NDMA. A control group simultaneously received phosphate buffer vehicle. Tumours related to instillation appeared principally in the respiratory tract and the liver. Over the entire lifespan of the animals tumour incidence rates in the respiratory tract were 100% in both the NDEA groups, 6% in both NDMA groups and 8% in the control group. The total incidences of liver tumours were 6% in the 0.75 mg NDMA group, 19% in the 1.5 mg NDMA group, zero in the NDEA groups, and 4% in the control group. These results indicate that, when administered by this route, NDEA is a much more potent carcinogen in the respiratory tract than is NDMA but NDMA alone seems to be carcinogenic to the liver, at a total dosage of 1.5 mg.

Comparative study on the carcinogenicity of N-nitrosodiethylamine, N-nitrosodimethylamine, N-nitrosomorpholine, N-nitrosopyrrolidine and N-nitrosodi-n-propylamine to the lung of Syrian golden hamsters following intermittent instillations to the trachea.

N-Nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), N-nitrosomorpholine (NMOR), N-nitrosopyrrolidine (NPYR) and N-nitrosodi-n-propylamine (NDPA) were instilled into the lungs of male Syrian golden hamsters by intratracheal instillations once a week for 15 weeks. The total doses given were 1.5 mg of each drug. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During the total lifespan, tumor incidence rates in the respiratory organs were 100% in the NDEA group, 6% in the NDMA group, 43% in the NMOR group, 0% in the NPYR group, 72% in the NDPA group and 4% in the control group. The incidence rates in the liver were 19% in the NDMA group and 4% in the NPYR group. No liver tumors developed in the other groups. The carcinogenic potencies of these N-nitroso compounds to the respiratory organs was provisionally estimated to be in the following order: NDEA greater than NDPA greater than NMOR greater than NDMA = NPYR, at the 1.5 mg dosage level. However, the difference in the rates of tumor incidence between the NDMA or NPYR group and the control group was not significant.

Comparison of XAD-2 column and blue cotton batch techniques for isolation of metabolites of 2-amino-3-methylimidazo[4,5-f]quinoline.

In studies on the metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the rat, two methods were used to concentrate IQ and its metabolites in urine: XAD-2 columns and blue-cotton extraction. These methods were compared as to the total recovery of 14C-label and the results of high-performance liquid chromatography (HPLC) of the main metabolites. In the HPLC analysis, three major peaks in the polar region and two adjacent peaks in the nonpolar region having radioactivity were found in the urine from rats given 14C-IQ. XAD-2 columns adsorbed approximately 65% and blue cotton 23% of the applied isotope from the urinary metabolites. Both methods efficiently adsorbed and totally released the relatively nonpolar compounds in a mixture of metabolites, including the compound administered, IQ. However, they failed to retain the more polar metabolites. Thus, both the XAD-2 column and blue cotton adsorption techniques may be useful mainly to concentrate nonpolar compounds from larger volumes of aqueous solutions.

Ingestion of parsley inhibits the mutagenicity of male human urine following consumption of fried salmon.

The urinary mutagenicity of 3 nonsmoking, healthy men was investigated after strictly defined meals by means of the Ames Salmonella/microsome test. When the subjects ate 150 g of fried salmon at one meal, a potent mutagenicity of almost 5000 revertants of TA98 strain was present in all 6-h urine samples. On the other hand, less than 2500 revertants was present in the urine when the subjects simultaneously consumed 70 g of parsley and 150 g of fried salmon. Thus, the protection against mutagenicity affected by parsley warrants further attention.

Some secular changes in body height and proportion of Japanese medical students.

Anthropometric dimensions of 738 medical students at Kyushu University in Japan were analyzed to determine secular changes of height and body proportions during a 20-year period. Since 1961, means of standing height, leg length, and ratio of leg length to standing height have increased, although the rate of increase from 1971 to 1981 has been rather slow. On the contrary, the mean sitting height X 100/standing height has declined during this same period. Compared with data on the Japanese general population, the medical students were considerably taller, but the difference has decreased.

Mutagenicity of human urine after the consumption of fried salted salmon.

Mutagenicity in the urine of four non-smoking individuals who had eaten salted salmon cooked at home for both lunch and supper was monitored by means of Salmonella/microsome mutagenicity tests. Extracts from fresh and salted salmon had the same level of mutagenicity after being cooked for 10 min at 200 degrees C, but no activity was detected before cooking. Salmonella strains TA98 and TA1538 were equally sensitive to the mutagens and required metabolic activation. No mutagenicity was shown with TA100 and TA1535. Urine samples were tested using a concentrate prepared by means of an XAD-2 resin column. Mutagenicity was detected mainly in urine excreted during 4-5 hr after the ingestion of cooked salmon, but only weak mutagenicity, or none at all, was detected in the urine after the ingestion of vegetables. The levels of urinary mutagenicity due to salmon consumption were not affected when cabbage was eaten simultaneously. The excretion of mutagenic substances was completed within about 20 hr, and there were almost no mutagens in the urine 24 hr after the ingestion of cooked salmon.

Mutagenicity of urine from young male smokers and nonsmokers.

The mutagenicity of urine from a healthy population of young adult men (average age of 23 years), including 61 smokers and 107 nonsmokers, was investigated with the Salmonella/microsome test using the tester strain S. typhimurium TA98. In quantifying the assay, the use of dichloromethane was suitable for eluting the mutagenicity of smokers' urine from the XAD-2 resin column. We assayed mutagenicity in condensates of such dichloromethane eluates and found that the mutagenicity of smokers' urine was significantly higher than that of nonsmokers' urine. In the smokers' group, correlation coefficient between "the mutagenicity of the urine" and "the actual number of cigarettes smoked on the day of urine collection" or "the average number of cigarettes smoked per day" was statistically significant at 0.266 or 0.454, respectively. Our results suggest a correlation between the increase of mutagens in urine and smoking habits.

Tumorigenicity of arsenic trioxide to the lung in Syrian golden hamsters by intermittent instillations.

The tumorigenicity of arsenic trioxide was investigated in female Syrian golden hamsters which were given a total of 5.25 mg or 3.75 mg as arsenic by intratracheal instillations once a week. As controls, hamsters were treated with the vehicle, phosphate buffer solution. During the total life span, 3 lung adenomas were manifested in 10 hamsters or 2 lung adenomas in another 20 hamsters after 15 instillations of arsenic, while no lung tumor was detected among 35 hamsters in 2 control groups. The results show that arsenic trioxide is tumorigenic to the lung of Syrian golden hamsters.

Arsenic metabolites in urine and feces of hamsters pretreated with PCB.

High pressure liquid chromatography and graphite tube atomizing atomic absorption spectrometry were used to quantify monomethyl arsonic acid (MMA), dimethyl arsinic acid (DMA), and inorganic arsenic (IA: arsenite plus arsenate) in the urine and feces of male and female hamsters pretreated with a single ip injection of PCB (100 mg/kg) and 4 days later given a single po dose of arsenite (10 mg As/kg). Approximately 17 to 23% and 35 to 63% of the arsenic given was eliminated in the urine and feces, respectively, during the 5 days after the administration of arsenic. Both DMA and MMA were found in the urine but only MMA was detected in the feces, as methylated metabolite. Fecal excretion of arsenic was significantly larger in female than in males. PCB influenced the metabolism of arsenic by significantly increasing the proportion of DMA excreted into the urine of female hamsters during the 5 days after the arsenic administration, but did not alter the total amount of arsenic metabolites in any group of male or female hamsters. PCB did not affect the cumulative amounts of fecal arsenic in any group, although the excretion in the PCB-treated group of females reached the maximum level 1 day earlier than in the controls. These results suggest that the metabolism of arsenic may be regulated by certain sex-relating factors which are influenced by PCB.

Outbreak of chronic arsenic poisoning among retired workers from an arsenic mine in Japan.

Retired former workers of Matsuo Arsenic Mine of Miyazaki prefecture in Japan were subjected to extensive medical examination. The number of retired workers subjected to examination were 61 of 208 workers who were engaged in the works of the mine and were tracked down by the work rolls. These workers left the mine more than 15 years prior to the time of the examination. The main works in the mine were classified as mining, dressing of ores, refining, and clerical work. Several findings such as arsenodermatitis, depigmentation, performation of nasal septum, hyposmia, anosmia, and peripheral nervous disturbance attributed to exposure to arsenic were observed in 9 of 21 roasters who often worked in the arsenic kitchen. No characteristic findings of arsenic poisoning, that is, gastrointestinal disturbance, disorder of the cardiovascular system, hematopoietic disorders, or liver disturbance were observed in the retired workers. Another notable finding was that 8 cases diagnosed as pneumoconiosis were found in 18 miners.