Studies in vivo to investigate the status of 4-N-pyrrolidinylazobenzene as a pure cancer initiating agent to the rat liver.
4-N-Pyrrolidinylazobenzene (4N) has been described sequentially as a potential rat hepatocarcinogen, a non-hepatocarcinogen to the rat, a possible pure initiating agent to the rat liver and as unlikely to be either a rat hepatocarcinogen or a cancer initiating agent. Given the importance of defining a pure initiating agent to the rodent liver we have conducted experiments to evaluate the status of 4N in this respect. By histopathological criteria 4N is non-hepatotoxic to the rat liver following daily oral gavage for 6 weeks, but it can be detected unbound in the rat liver following a single exposure via oral gavage and methaemoglobin is evident in peripheral blood. In addition, it fails to bind covalently to hepato-proteins or to initiate unscheduled DNA synthesis in the rat liver following oral dosing. Under similar conditions of bioassay, the rat liver carcinogen 3'-methyl-4-dimethylaminoazobenzene (3'M) gave a positive response on each count. Further, no evidence of histopathological change was observed in the rat liver following daily intraperitoneal injection of 4N for 2 weeks. It is concluded that 4N is both non-toxic and non-genotoxic to the rodent liver in vivo in all respects studied, and that it is therefore very unlikely to possess cancer initiating activity in this tissue.
D000818:Animals; D001391:Azo Compounds / Q000633:toxicity*; D002273:Carcinogens; D004260:DNA Repair / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D008749:Methyldimethylaminoazobenzene; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D001391:Azo Compounds; D002273:Carcinogens; C031836:4-N-pyrrolidinylazobenzene; D008749:Methyldimethylaminoazobenzene