Lack of genetic and in vitro metabolic activity of potently carcinogenic azoxyalkanes.
4 carcinogenic azoxyalkanes (azoxymethane, azoxymethane and the 2 mixed methyl-ethyl compounds) were examined for activity in the Salmonella histidine reversion assay and in a lambda-lacZ prophage induction assay. Because azoxyalkanes are isomeric with nitrosodialkylamines, and might be expected to generate the same active intermediates, their biological activity was investigated under conditions which would allow direct comparison with these well-studied carcinogens. However, none of the azoxyalkanes, which are liver carcinogens, showed significant activity in either microbial assay in the presence of liver S9. In addition, metabolism studies with liver microsomes or hepatocytes indicated that the compounds were metabolized only to a small extent, if at all, under the conditions examined. This inactivity of the azoxyalkanes contrasts with the considerable activity in these assays - and the substantial metabolism - of the isomeric nitrosodialkylamines, also liver carcinogens. These results suggest that the carcinogenic action of azoxyalkanes proceeds through alternative metabolic pathways that are not adequately modeled by the assays and in vitro conditions used here.
Lijinsky
W
W
Andrews
A W
AW
Elespuru
R K
RK
Farrelly
J G
JG
D000818:Animals; D001391:Azo Compounds / Q000378:metabolism / Q000494:pharmacology*; D001397:Azoxymethane / Q000378:metabolism / Q000494:pharmacology; D010582:Bacteriophage lambda / Q000187:drug effects; D001711:Biotransformation; D002273:Carcinogens / Q000494:pharmacology*; D006224:Cricetinae; D008099:Liver / Q000378:metabolism*; D008242:Lysogeny; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D009154:Mutation; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D001391:Azo Compounds; D002273:Carcinogens; D009153:Mutagens; D001397:Azoxymethane