Mutagenesis assays on urines produced by patients administered adriamycin and cyclophosphamide.
The XAD-2 resin concentration/elution system for concentration of mutagens contained in urines was optimized for cancer patients who had been administered such antineoplastic agents as adriamycin (ADR; doxorubicin), cyclophosphamide (CP), methotrexate, vincristine, and 5-fluorouracil. In the reverse mutation assay, Salmonella typhimurium strains TA1535 and TA98 differentiated between CP (with S9 fraction) and ADR (without S9), respectively. No dose-response for CP was observed. There was a dose-response to ADR by TM677 in the presence of S9 using a forward mutation assay. However, while the reverse mutation assays successfully detected ADR and CP administration in the presence of each other in terms of urine mutagenicity, the forward mutation assay did not, since unidentified CP metabolites were also detected in the latter. None of these systems detected mutagenic urines from tobacco smokers, although reaction of these urines with beta-glucuronidase allowed this type of source to be detected also.
Department of Environmental Health, University of Cincinnati, Ohio.
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Newman
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Hee
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Schoeny
D000818:Animals; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000652:urine; D004317:Doxorubicin / Q000009:adverse effects* / Q000652:urine; D004359:Drug Therapy, Combination; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy; D008113:Liver Neoplasms / Q000188:drug therapy; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests; D009154:Mutation; D051381:Rats; D011919:Rats, Inbred Strains; D012475:Salmonella / Q000187:drug effects; D013429:Sulfatases / Q000378:metabolism
D004317:Doxorubicin; D003520:Cyclophosphamide; D013429:Sulfatases; D005966:Glucuronidase