Studies in vivo to investigate the status of 4-N-pyrrolidinylazobenzene as a pure cancer initiating agent to the rat liver.

Abstract

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.

• Authors: J Ashby, B M Elliott, W Keen, E Riley
• Journal: Cancer letters (Cancer Lett) Vol. 27 Issue 1 Pg. 115-22 (May 1985) ISSN: 0304-3835 [Print] Ireland
• PMID: 4005822 (Publication Type: Journal Article)

Chemical References

• Azo Compounds
• Carcinogens
• 4-N-pyrrolidinylazobenzene
• Methyldimethylaminoazobenzene

Topics

• Animals
• Azo Compounds (toxicity)
• Carcinogens
• DNA Repair (drug effects)
• Liver (metabolism)
• Liver Neoplasms, Experimental (chemically induced)
• Male
• Methyldimethylaminoazobenzene
• Rats
• Rats, Inbred Strains
• Structure-Activity Relationship