Megalocytosis and other abnormalities expressed during proliferation in regenerating liver of rats treated with methylazoxymethanol acetate prior to partial hepatectomy.

Rats were partially hepactectomized at various intervals after receiving a single injection of the carcinogen, methylazoxymethanol acetate. In treated rats, there was a delay and a reduction in the peak response of hepatic DNA synthesis. At 48 hr after partial hepatectomy, following completion of the first mitoses, almost all hepatocytes were enlarged (megalocytes) and many contained enlarged nuclei. Although at 7 days after the hepatectomy many megalocytes could still be found in centrilobular zones, the majority of the hepatocytes were of normal size or smaller. Abnormal anaphase and telophase figures containing chromosomal bridges and acentric fragments were found during the period of regeneration. In addition, discrete nests of small cells with increased cytoplasmic basophilia were evident. Megalocytes also appeared when rats were partially hepatectomized as late as 26 weeks after injection of the carcinogen. These results show that a single dose of methylazoxymethanol acetate can affect almost all hepatocytes and that latent effects persist for long periods of time.