Comparison in C3H and C3B6F1 mice of the sensitivity to diethylnitrosamine-initiation and phenobarbital-promotion to the extent of cell proliferation.
The ability of diethylnitrosamine (DENA) to initiate and phenobarbital to promote altered-hepatocyte foci and hepatocellular carcinomas in C3H and C3B6F1 (C3H x C57BL/6) mice was compared to the extent of cell proliferation. Fifteen day old female mice received DENA (16 mg/kg, i.p.) or the vehicle control followed at weaning with 500 p.p.m. sodium phenobarbital in their drinking water until killed at 161 days of age. Six days prior to death each mouse had implanted an osmotic minipump containing 30 mg/ml bromodeoxyuridine in order to measure cell proliferation as the labeling index of bromodeoxyuridine incorporation into newly replicated DNA. C3H mice were more susceptible to DENA than C3B6F1 mice, 54.1 versus 0.57 adenomas/mouse respectively, and phenobarbital increased the yield of altered-hepatocyte foci in C3H mice. Hepatocellular adenomas had a greater bromodeoxyuridine labeling index than altered-hepatocyte foci, which was greater than non-involved/normal hepatocytes. In DENA-initiated C3H and C3B6F1 mice, phenobarbital increased the labeling index in eosinophilic foci, while decreasing the labeling index in normal/non-involved hepatocytes with/without DENA initiation. However, the level of cell proliferation in normal/non-involved hepatocytes, foci and adenomas was lower in C3H mice than in C3B6F1 mice. Thus, the level of cell proliferation did not correlate to the higher yield of foci and tumors in C3H mice. The results are consistent with the strain sensitivity to DENA-initiation and to phenobarbital-promotion correlating to the ratio of the labeling index in the foci to the labeling index in non-involved hepatocytes. An increase in this labeling index ratio for cell proliferation indicates that the foci are selectively stimulated to proliferate resulting in a greater expansion of the population of precancerous cells in the liver.
Pereira
M A
MA
Environmental Health Research and Testing Inc., Lexington, KY 40503.
D000236:Adenoma / Q000139:chemically induced*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004052:Diethylnitrosamine; D005260:Female; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains / Q000502:physiology*; D010634:Phenobarbital / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013045:Species Specificity
D004052:Diethylnitrosamine; D010634:Phenobarbital