Amplified response to phenobarbital promotion of hepatotumorigenesis in obese yellow Avy/A (C3H x VY) F-1 hybrid mice

Carcinogenesis
G L WolffJ J Chen

Abstract

Mottled yellow Avy/A and agouti A/a (C3H x VY) F-1 hybrid male mice were fed untreated control diet or diet with a target dose of 500 p.p.m. sodium phenobarbital (PB) for 17-19 months. No differences in prevalence of hepatocellular adenomas or carcinomas were found between untreated yellow and agouti mice. PB treatment increased prevalence of adenomas but decreased prevalence of carcinomas. No difference in enhancement of adenoma formation by PB was observed between yellow and agouti mice bearing single adenomas. However, the proportion of PB-treated yellow mice bearing multiple adenomas (66%) was much greater than the proportion of analogous agouti mice (18%). Fatty changes in the periportal area of the liver and focal cytoplasmic vacuolization were induced to a much greater extent in PB-treated yellow mice than among treated agoutis. PB increased the prevalence and severity of focal areas of chronic inflammation in the liver considerably more in agouti than in yellow mice. The possible relation of this finding to the altered immune responses of obese yellow mice remains to be determined. The results of this study suggest that the use of yellow Avy/A and agouti A/a (C3H x VY) F-1 hybrid mice in carcinogenicity assays make make...Continue Reading

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