Studies on the hyperplastic responsiveness of binucleated rat hepatocytes.
Rats were dosed by gavage for 28 days with 25 mg/kg of 3'methyl-4-dimethylaminoazobenzene (3'M) followed by 4 days dosing with 0.5 ml/100 g corn oil. Livers from animals were taken at intervals during the 4 days of corn oil dosing and examined for S-phase activity and nuclearity. The treatment regime caused an increase in the proportion of diploid (2N) cells in the hepatocyte population, a decrease in the proportion of binucleated (2 x 2N) cells of approximately 50%, and induced an increase in cell replication. A second group of rats was dosed for 28 days with 0.5 ml/100 g corn oil followed by 4 days administration of 25 mg/kg methylclofenapate (MCP). Analysis of hepatocytes taken during the MCP treatment revealed that there was acute hyperplasia, involving mainly the 2 x 2N hepatocytes, resulting in a reduction of approximately 50% of the 2 x 2N cells and an accompanying increase in the proportion of 4N cells. When a third group was given 3'M for 28 days followed by 4 days administration of MCP, there was, at the outset of MCP dosing, a hepatocyte population typical of 3'M dosed animals, with an elevated proportion of 2N cells and a 2 x 2N fraction that was reduced to approximately 50% of control levels. During the 4 days of MCP dosing there was a wave of hyperplasia involving S-phase activity in the remaining 2 x 2N hepatocytes. The proportion of 2 x 2N cells decreased further during this period and there was a concomitant increase in 4N cells. The 2N fraction, already elevated, was not further affected. These results indicate that both genotoxic and non-genotoxic hepatocarcinogens induce acute changes in the rat hepatocyte population that involve 2 x 2N cells, and that the effects appear to involve separate sub-populations of 2 x 2N hepatocytes.
Styles
J A
JA
ICI Central Toxicology Laboratory, Alderley Park, Near Macclesfield, Cheshire, UK.
Bybee
A
A
Pritchard
N R
NR
Kelly
M D
MD
D000818:Animals; D002087:Butyrates / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D002992:Clofenapate / Q000633:toxicity*; D006965:Hyperplasia / Q000139:chemically induced; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008749:Methyldimethylaminoazobenzene / Q000633:toxicity*; D051381:Rats; D004124:p-Dimethylaminoazobenzene / Q000633:toxicity*
D002087:Butyrates; D002992:Clofenapate; D008749:Methyldimethylaminoazobenzene; D004124:p-Dimethylaminoazobenzene