Age related variations of hepatocarcinogenic effect of azo dye (3'-MDAB) as linked to the level of hepatocyte polyploidization.
Four-week-old CBA mice fed a diet containing the hepatocarcinogenic azo dye 3'-MDAB showed a rapid polyploidization of hepatocytes, a sharp increase of two liver-specific acid soluble non-histone proteins (LSP 1 and 2) and induction of hepatomas between 44 and 52 weeks of the regimen. More mature 18-week-old mice fed the same diet did not develop induced hepatocarcinogenesis after 55 weeks of the regimen. Interruption of the azo dye regimen showed that the increase of LSP 1 and 2 was reversible, whereas the carcinogenic effect and polyploidization were irreversible. Sprague-Dawley rats were more sensitive to the carcinogenic effect of the azo dye regimen. It is suggested that the higher resistance of older mice to the carcinogenic effect could be linked to the higher level of hepatocyte polyploidization and that the increase of LSP 1 and 2 is relevant to the toxic effect of the azo dye.
Medvedev
Z A
ZA
Genetics Division, National Institute for Medical Research, Mill Hill, London, U.K.
Crowne
H M
HM
Medvedeva
M N
MN
D000375:Aging / Q000502:physiology*; D000818:Animals; D006657:Histones / Q000032:analysis; D008099:Liver / Q000032:analysis / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D008297:Male; D008749:Methyldimethylaminoazobenzene / Q000633:toxicity*; D051379:Mice; D011123:Polyploidy; D011506:Proteins / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D004124:p-Dimethylaminoazobenzene / Q000031:analogs & derivatives*
D006657:Histones; D011506:Proteins; D008749:Methyldimethylaminoazobenzene; D004124:p-Dimethylaminoazobenzene