Increased mutagenicity of chloroethylnitrosoureas in the presence of a rat liver S9 microsome mixture.
The mechanism for an enhanced effect of Aroclor 1254-induced Sprague-Dawley rat liver 9,000 x g supernatant (S9) microsome preparation on the mutagenicity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2-chloroethyl)-3-cyclohexyl-N-nitrosourea (CCNU), and 2-[3-(2-chloroethyl)-3-nitrosoureido]-2-deoxy-D-glucopyranose (chlorozotocin) for Salmonella typhimurium strain TA1535 was studied. Although all three compounds were direct-acting mutagens, rat liver S9 increased the mutagenic response to BCNU, CCNU, and chlorozotocin. The enhanced mutagenic effect was independent of NADPH. Heat-denatured S9 enhanced the mutagenicity of BCNU and CCNU, but not that of chlorozotocin. Mutagenic enhancement, however, was less than that observed with untreated S9. The substitution of extractable S9 lipid and bovine serum albumin for S9 in the reaction mixture resulted in an enhanced mutagenicity of CCNU with little or no effect on BCNU or chlorozotocin mutagenicity. These results suggest that the enhanced mutagenicity of CCNU, and possibly that of BCNU, in the presence of S9 was due in part to nonspecific factors that are present in the S9 preparation.
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001711:Biotransformation; D002330:Carmustine / Q000633:toxicity*; D020111:Chlorodiphenyl (54% Chlorine); D003520:Cyclophosphamide / Q000633:toxicity*; D008130:Lomustine / Q000633:toxicity*; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D009607:Nitrosourea Compounds / Q000633:toxicity*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects; D013311:Streptozocin / Q000031:analogs & derivatives* / Q000633:toxicity
D001140:Aroclors; D009153:Mutagens; D009607:Nitrosourea Compounds; D020111:Chlorodiphenyl (54% Chlorine); C007028:chlorozotocin; D013311:Streptozocin; D008130:Lomustine; D003520:Cyclophosphamide; D002330:Carmustine