Metabolism of benzo(a)pyrene by aortic subcellular fractions in the setting of abdominal aortic aneurysms.

As exposure to polycyclic aromatic hydrocarbons (PAHs; a family of environmental toxicants) have been implicated in cardiovascular diseases, the ability of the aortic tissue to process these toxicants is important from the standpoint of abdominal aortic aneurysms and atherosclerosis. Benzo(a)pyrene (B(a)P), a representative PAH compound is released into the environment from automobile exhausts, industrial emissions, and considerable intake of B(a)P is also expected in people who are smokers and barbecued red meat eaters. Therefore, knowledge of B(a)P metabolism in the cardiovascular system will be of importance in the management of vascular disorders. Toward this end, subcellular fractions (nuclear, cytosolic, mitochondrial, and microsomal) were isolated from the aortic tissues of Apo E mice that received a 5 mg/kg/week of B(a)P for 42 days and 0.71 mg/kg/day for 60 days. The fractions were incubated with 1 and 3 µM B(a)P. Post incubation, samples were extracted with ethyl acetate and analyzed by reverse-phase HPLC. Microsomal B(a)P metabolism was greater than the rest of the fractions. The B(a)P metabolite levels generated by all the subcellular fractions showed a B(a)P exposure concentration-dependent increase for both the weekly and daily B(a)P treatment categories. The preponderance of B(a)P metabolites such as 7,8-dihydrodiol, 3,6-, and 6,12-dione metabolites are interesting due to their reported involvement in B(a)P-induced toxicity through oxidative stress.

Metabolism of the environmental toxicant benzo(a)pyrene by subcellular fractions of human ovary.

Knowledge of the ability of the female reproductive system to metabolize environmental chemicals is critical not only from the standpoint of toxicity but also from infertility risk assessment. Benzo(a)pyrene (BaP) is a toxicant that is released into the environment from automobile exhausts, cigarette smoke, burning of refuse, industrial emissions, and hazardous waste sites. In exposed animals, BaP becomes activated to reactive metabolites that interfere with target organ function and as a consequence cause toxicity. Studies on animal models conducted in our laboratories and those of others have shown that BaP possess endocrine disrupting properties. Thus, this chemical has the potential to cause infertility and cancers in the female genital tract. An understanding of BaP metabolism in the female reproductive system will be of importance in the diagnosis and management of female fertility as well as cancers in the reproductive tissues. Therefore, the objective of our study was to examine the metabolism of BaP by human ovarian subcellular fractions. Human ovary samples (eight individuals) were obtained from postoperative tissue removed from subjects with uterine tumors. Subcellular fractions (nuclear, cytosolic, mitochondrial, and microsomal) were prepared by differential centrifugation. BaP (1 µM and 3 µM) was individually incubated with individual subcellular fractions for 15 min and the products were analyzed by high-performance liquid chromatography. Among the different fractions tested, microsomal BaP metabolism was higher than the rest of the fractions. The BaP metabolites identified were as follows: BaP-9,10-diol, BaP-4,5-diol, BaP-7,8-diol, 9(OH) BaP, 3(OH) BaP, BaP-1,6-dione, BaP-3,6-dione, and BaP-6,12-dione. Of interest was the presence of DNA-reactive metabolites such as BaP-3,6-dione, BaP-6,12-dione, and BaP 7,8-diol, which have been implicated in the causation of infertility and cancer. Our results indicate that women who are exposed to BaP via cigarette smoke, occupational settings, and diet are more likely at a larger risk of this toxicant-induced infertility and cancer than others.

Monitoring of oxidative stress in nurses occupationally exposed to antineoplastic drugs.

Antineoplastic drugs (ANDs) have been in clinical usage for more than five decades. The nonselective mechanism of action of ANDs between cancerous and noncancerous cells had well documented side effects such as acute symptoms, reproductive health issues, and potential cancer development in healthcare workers as a result of occupational exposure. The anticancer mechanism of ANDs is the generation of reactive oxygen species (ROS) which are responsible for various side effects in patients undergoing chemotherapy and the healthcare personnel occupationally exposed to them. ROS have potential to damage lipids, DNA, proteins, and so on leading to oxidative stress condition. The aim of this study was to evaluate the possible oxidative stress effect of antineoplastic drugs in nurses who routinely handle ANDs in an oncology hospital in south India. Malondialdehyde levels, reduced glutathione content, and glutathione S-transferase activity were analyzed in serum collected from 60 female nurses handling ANDs and compared with equal number of healthy volunteers matched by age and sex except AND exposure. The results showed statistically significant (P < 0.05) increase in malondialdehyde levels in the serum of exposed nurses. However, glutathione content and glutathione S-transferase activity was significantly decreased in these nurses. Our study suggests that the nurses occupationally exposed to ANDs were susceptible to the oxidative stress and emphasizes the need for a harmonized safe handling approach that assures minimal risk to the working nurses.

Determination of genetic damage and urinary metabolites in fuel filling station attendants.

Fuel (diesel and petrol) constitutes a complex mixture of volatile flammable liquid hydrocarbons among them benzene (BZ), toluene (TOL), and xylene (XYL) are considered to be the most hazardous, predominantly BZ because of its carcinogenic potency. Exposure to these compounds may have an impact on the health of the exposed subjects. Hence, genotoxicity and quantitative analysis of these compounds was performed in blood and urine samples of 200 workers exposed to fuel in filling stations and compared to controls. The level of genetic damage was determined by micronucleus test (MNT) in buccal epithelial cells (BEC) and chromosomal aberrations (CA) assay in peripheral blood lymphocytes (PBL) of fuel filling station attendants (FFSA) and compared to a matched control group. Urine analysis for BZ and its metabolites, phenol (Ph), trans, trans-Muconic Acid (t, t-MA), and S-Phenyl Mercapturic Acid (S-PMA) was done in all the study subjects. The results of our study revealed that exposure to BTX in petrol vapors induced a statistically significant increase in the frequency of micronuclei (MN) and CA in the exposed subjects than in controls (P < 0.05). There was a significant rise in the levels of urinary BZ, Ph, t, t-MA, and S-PMA in the exposed subjects. Our study highlights the significance of MNT, CA, and urinary metabolites as potential biological exposure indices of genetic damage in FFSA. This study suggests the need for regular monitoring of FFSA for possible exposure to BTX as a precautionary and preventive step to minimize exposure and reduce the associated health risks.

Genotoxicity evaluation in workers occupationally exposed to lead.

Lead (Pb) is a widely used heavy metal with a broad industrial usage. Nevertheless, Pb is a serious public health issue as it is one of the most widespread environmental and industrial toxins. The aim of this investigation was to assess the genotoxicity of Pb using the comet assay, micronucleus (MN) and chromosomal aberrations (CA) test. Blood and urinary Pb content, levels of delta-aminolevulinic acid dehydratase in the erythrocytes (E-ALAD) and delta-aminolevulinic acid in urine (U-ALA) were determined. The exposure associated oxidative stress was also studied. The study group comprised of 90 male Pb recovery unit workers and 90 matched controls. The results indicated that the exposed workers had a significantly higher mean comet tail length than that of controls (P<0.05). Analysis of micronuclei in buccal epithelial cells (BEC's) and peripheral blood lymphocytes (PBL) revealed that there was a significant increase in frequency of MN in exposed subjects than controls. The frequency of aberrant metaphases was also found to be significantly elevated in the Pb exposed workers. The levels of antioxidant enzymes were relatively reduced (P>0.05) while the rate of lipid peroxidation was higher in the exposed subjects. Blood and urinary Pb concentrations were found to be higher in exposed workers than in controls. E-ALAD levels were reduced and U-ALA levels were elevated in the exposed subjects in comparison to controls. Results of analysis, taking the confounding factors into consideration provide evidence for the association of Pb exposure and genotoxicity, and predict the increased risk of cancer to the exposed workers. In view of the observed results, it can be strongly concluded that the workers comprise the risk group and adequate safety, precautionary and preventive measures could only minimize exposure and the related health hazards.

Genetic damage in wood dust-exposed workers.

Exposure to wood dust is common in carpentry workshops. Wood dust is known to be a human carcinogen, with a very high relative risk of adenocarcinoma of the nasal cavities and paranasal sinuses. The goal of this investigation was to conduct genotoxicity monitoring of carpenters involved in wooden furniture industry in order to test possible wood dust-induced genotoxic effects due to occupational exposure. The level of genetic damage was determined by comet, micronucleus and chromosomal aberration (CA) assays in peripheral blood lymphocytes (PBL) of 60 carpentry workers. In addition, the micronucleus test in buccal epithelial cells was carried out in the same subjects. Total antioxidant enzyme activities were measured by the indices: superoxide dismutase, glutathione peroxidase and catalase. A group of 60 non-exposed subjects matched by age, smoking and alcohol consumption habits were chosen as controls. The effect of age, smoking, alcohol consumption and duration of exposure was also analysed in the subjects of the present study. The results showed a statistically significant increase in mean DNA damage by comet assay, micronuclei frequency in buccal cells as well as PBL and frequency of CA in the exposed workers when compared to controls (P < 0.05). Analysis of the data showed that all the confounding factors had a significant effect on DNA damage and micronucleus frequency in buccal epithelial cells and PBL. Smoking and alcohol consumption did not have any significant effect by chromosomal aberration test. Antioxidant enzyme levels significantly decreased in the exposed subjects. Our findings indicate enhanced levels of genotoxicity in carpenters. Hence, these workers may have an increased cancer risk.

Genotoxicity assessment in oncology nurses handling anti-neoplastic drugs.

Many anti-neoplastic drugs are used globally during chemotherapy in the treatment of cancer. However, occupational exposure to anti-cancer drugs can represent a potential health risk to humans. Investigations on the genotoxicity of these drugs are inconsistent. Further, information on the genotoxic potential of anti-neoplastic drugs in medical personnel from India is not available. Hence, the aim of this study was to carry out genotoxicity monitoring of nurses from the oncology department of a hospital in South India, occupationally exposed to anti-neoplastic drugs under routine working conditions. The level of genome damage was determined in whole blood with the comet assay as well as micronucleus test (MNT) and in buccal epithelial cells with MNT alone of 60 nurses handling anti-neoplastic drugs and 60 referents matched for age and sex. Urinary cyclophosphamide (CP), used as a marker for drug absorption, was also measured in the urine of the nurses. The DNA damage observed in the lymphocytes of exposed nurses was significantly higher than the controls. Similarly, a significant increase in micronuclei (MN) frequency with peripheral blood lymphocytes and buccal cells was observed in the exposed nurses compared to controls (P < 0.05). Multiple regression analysis showed that occupational exposure and age had a significant effect on mean comet tail length as well as on frequency of MN. The mean value of CP in urine of the nurses handling anti-neoplastic drugs was (mean +/- standard deviation; 0.44 +/- 0.26 microg/ml). Our study has shown that increased genetic damage was evident in nurses due to occupational exposure to anti-neoplastics. This data corroborate the need to maintain safety measures to avoid exposure and the necessity of intervention in the case of exposure when using and handling anti-neoplastic drugs.

Genotoxic evaluation of workers employed in pesticide production.

Pesticides are widely used throughout the world in agriculture to protect crops and in public health to control diseases. Nevertheless exposure to pesticides can represent a potential risk to humans. Pesticide manufacturing unit workers are prone to possible occupational pesticide exposure. Therefore, this study was performed to evaluate the genotoxic effect of pesticide exposure in these workers. In the present investigation 54 pesticide workers and an equal number of control subjects were assessed for genome damage in blood lymphocytes utilizing the chromosomal aberration analysis and the buccal epithelial cell by adopting the micronucleus test. The results suggested that pesticide workers had a significantly increased frequency of chromosomal aberrations when compared with controls (mean+/-S.D., 8.43+/-2.36 versus 3.32+/-1.26; P<0.05). Similarly, the pesticides exposed workers showed a significant increase in micronucleated cells compared with controls (1.24+/-0.72 versus 0.32+/-0.26; P<0.05). Analysis of variance revealed that occupational exposure to pesticides had a significant effect on frequency of micronuclei (P<0.05), whereas smoking, age, gender and alcohol consumption had no significant effect on genetic damage (P>0.05). However, no association was found between years of exposure, smoking, age, gender, alcohol consumption and higher levels of genetic damage as assessed by the chromosomal aberration assay (P>0.05). Our findings indicate that occupational exposure to pesticides could cause genome damage in somatic cells.

Evaluation of genetic damage in operating room personnel exposed to anaesthetic gases.

Information on potential genetic damage in humans after exposure to waste anaesthetic gases in Indian hospitals is scarce. To evaluate the possible genotoxic effects of waste anaesthetic gases, the chromosomal aberrations analysis and comet assay were studied in peripheral blood lymphocytes in 45 operating room personnel currently employed at a hospital in South India. In addition, the micronucleus test on buccal epithelial cells was also carried out in the same subjects. The exposed group was compared with a group of 45 non-exposed group, matched by age, sex, alcohol consumption and smoking habits. The results showed a statistically significant increase in DNA damage by the comet assay in the exposed group. Chromosome aberrations and micronucleus frequencies also increased significantly in the study subjects in comparison to the controls. Analysis of variance showed that smoking had a significant effect on DNA mean tail length, whereas alcohol consumption, duration of exposure to anaesthetic agents, age and gender had no significant effect. All the confounding factors had significant effect by the micronucleus test. However, smoking, alcohol consumption, age, gender and years of exposure showed no significant effect by the chromosome aberrations test. The results of our study suggest that exposure to waste anaesthetic gases has the potential to cause changes in the human genome.