Detection of low levels of urinary mutagen excretion by chemotherapy workers which was not related to occupational drug exposures

Urine specimens from a total of 26 subjects who were either nurses, pharmacists, or pharmacy technicians engaged in the preparation, handling, or administration of cancer chemotherapeutic agents were analyzed for the presence of mutagenic substances. Assays were performed using bacterial strains TA98 and TA100 in the Salmonella/mammalian microsomal mutagenicity assay developed by Ames et al. (Mutat. Res., 31: 347-364, 1975). Findings were compared with results from similar assays of urine specimens for 38 hospital personnel not exposed to cancer chemotherapeutic agents. There was no evidence of an association between occupational exposure to chemotherapy drugs and the presence of mutagenic substances that could be detected by this assay procedure in either specimens of filter-sterilized urine or extracts of urine concentrated with XAD-2 resins. An association was observed, however, between smoking and increased urinary excretion of mutagens. None of the observed associations was changed substantially by statistical adjustment for the occupational category of the subject (nurse or pharmacist), hospital of employment, or values of concurrent solvent controls for the mutagenesis assays. Associations with occupational exposures were not changed by controlling for smoking history. In addition to the large increases for smokers, testing of extracts of urine from nonsmokers with bacterial strain TA98 yielded mutagenicity values that averaged about 50% higher than values for solvent controls. Similar small increases were observed in previous published reports of human urine mutagenicity assays using tester strains TA1538 and TA98. We found little evidence to suggest that the small increases observed for nonsmokers were associated with technical factors such as the presence in the extracts of histidine or other substances promoting bacterial growth or contamination of the specimens during collection or extraction procedures. Since it appears that technical factors can be excluded, we believe that the increases were associated with urinary excretion of low levels of mutagen by a high proportion of subjects tested. The lack of an association of mutagenicity with occupational exposure to chemotherapeutic drugs may have been due to protective measures at the hospitals surveyed and suggests that, with appropriate procedures, these agents can be administered in a manner such that human exposure cannot be detected using this approach.