Interactive effects of methyl-deficiency and dietary restrictionon liver cell proliferation and telomerase activity in Fischer 344 rats pretreated with aflatoxin B1

The effects of methyl-deficiency and dietary restriction (DR) on hepatic cell proliferation and telomerase activity was studied in male Fischer 344 rats pretreated with aflatoxin B1 (AFB1). Five-week-old rats were gavaged 5 days per week for 3 weeks with AFB1 (25 μg/rat per day) or solvent (100 μl 75% dimethylsulfoxide). Rats were then divided into four groups. Two groups were fed a methyl-sufficient (MS) diet either ab libitum (AL) or with DR. The other two groups were fed a methyl-deficient (MD) diet either AL or with DR. At 15, 20, and 32 weeks of age, hepatic cell proliferation, telomerase activity, and the number of glutathione S-transferase-P positive (GST-P+) foci were determined. DR reduced hepatic cell proliferation, while the MD diet and AFB1 pretreatment increased cell proliferation. Telomerase activity was decreased by DR and increased by the MD diet and AFB1 pretreatment. The same trend was observed with GST-P+ foci: in AFB1-pretreated rats, methyl deficiency increased the number of foci, while DR decreased the number. These results are consistent with a role of telomerase in hepatocarcinogenesis.