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Clastogenic activity in urine of individuals occupationally exposed to pesticides See, Raymond Hugh


Epidemiological evidence suggests that many human cancers may be attributed to environmental factors. Since the number of chemicals introduced into the environment is increasing at an alarming rate, measures must be taken to reduce human exposure. There is thus a growing need for the development of relevant and sensitive procedures for monitoring human exposure to environmental carcinogens and mutagens. The objective of this thesis was to evaluate the feasibility of using urine analysis to monitor individual exposure to pesticides. Pesticides are widely used chemicals in agriculture, and some are known to possess genotoxic properties. In this study, urine samples were collected from 21 orchardists (all non-smokers) in the Okanagan Valley when they were engaged in the application of pesticides during the fruit growing seasons in 1984 and 1985. As controls, urine was collected from these same individuals during the pre-spraying as well as the post-spraying seasons. In addition, 18 individuals from an agricultural research station in the Okanagan region (including 16 non-sprayers and 2 sprayers) were recruited to provide urine samples during the same time periods as the orchardists. As controls outside the fruit growing region, individuals from Vancouver and Grand Forks, B.C. were recruited to provide one urine specimen for this study. The urine samples were concentrated by reversed-phase high pressure liquid chromatography and then tested for their ability to induce chromosome aberrations (i.e., clastogenic activity) in cultured Chinese hamster ovary (CHO) cells. Furthermore, an attempt was made to examine the exfoliated urothelial cells for the presence of micronuclei as a potential in vivo indicator of damage by genotoxic constituents in the urine. Urine samples obtained from the orchardists 16 to 24 hours after pesticide application in 1984 resulted in levels of clastogenic activity undistinguishable from normal control limits. The failure to demonstrate increased clastogenic activity in the urine may have been due to (1) exposure to pesticides below the detection limits of the procedure, (2) the lack of genotoxicity in the agents sprayed, and (3) rapid pesticide metabolism and excretion in the urine. In the follow-up study of 1985, all urine voids were collected on the evening of the day of pesticide spraying (i.e., within 8 hours of exposure). Using this sampling protocol, the assay results showed that (1) urine samples collected from the orchardists and the agricultural research station workers during the non-spraying periods revealed no significant difference in clastogenic activity compared to the reference control group from Vancouver and Grand Forks, and (2) clastogenic activity of urine samples collected during the spraying period in 1985 was significantly elevated for the orchardist group (P<0.001; Tukey's non-parametric multiple comparisons test) but not for the agricultural research station personnel. The high urinary clastogenic activity found for the orchardists was attributed to heavy exposure to pesticides during the mixing, formulation and application process and the lack of compliance by the sprayers to wear full protective gear in hot weather. Cigarette smoking was another factor affecting urine clastogenicity together with pesticide exposure. Cigarette smokers from Grand Forks and the Okanagan agricultural research station demonstrated significantly higher urinary clastogenic activity than non-smokers (P<0.001; Mann-Whitney U test) . No dose-response relationship between the number of cigarettes smoked and urinary clastogenic activity was evident for the group of smokers assayed. All of the above effects were obtained without metabolic activation in vitro, suggesting that the clastogenic agents in the urine were direct-acting. In a large proportion of the urine samples tested, low but significant (relative to solvent controls) levels of clastogenic activity were observed in the urine of unexposed non-smokers, indicating the role of other factors in the appearance of urine clastogenicity. Urinary pH and creatinine did not differ among the study groups. No data were obtained from the analysis of micronuclei in exfoliated urothelial cells. The scarcity of cells among the subjects made it difficult to determine the frequency of micronucleated urothelial cells. On the basis of the present research, the monitoring of urine samples for genotoxicity appears to be a useful tool for assessing human exposure to environmental carcinogens and mutagens. Urine analysis is not only valuable in qualitatively demonstrating exposure to genetically hazardous agents, but is also a promising procedure for assessing the efficacy of preventive measures which are implemented to reduce further exposure.

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