Mitotic, Chromosomal, and Nucleolar Alterations Induced by Thioacetamide in Relation to the Mitotic Cycle After Partial Hepatectomv

Summary

Male Wistar rats were treated at various intervals after partial hepatectomy with single closes of thioacetamide (TAA) (150 mg/kg body wt) and killed 31 hours after surgery (one cell cycle completed). When the carcinogen was given 0.5–14 hours after hepatectomy (G₁ period), twofold higher labeling tritiated thymidine and mitotic indices were found. Between 16 and 24 hours (S phase), TAA inoculation resulted in striking mitotic (bridges), chromosomal (gaps, breakages), and nucleolar (anisonucleolinosis, i.e., the clumping of intranucleolar spherules containing ribonucleoprotein) abnormalities. They were 33, 30, and 25 times greater, respectively, than the control levels. The two largest chromosome pairs were altered in 60% of the abnormal metaphases. TAA-induced anisonucleolinosis was strongly promoted by Colcemid and vinblastine sulfate (VLB), although when administered separately, only VLB induced this abnormality. Both mitotic and nucleolar changes regressed at a relatively rapid rate during the first 50 days after carcinogen application. The high sensitivity of regenerating hepatocytes during the DNA synthetic phase to TAA is suggested.