Interactive effects of methyl-deficiency and dietary restrictionon liver cell proliferation and telomerase activity in Fischer 344 rats pretreated with aflatoxin B 1

Abstract

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 B 1 (AFB 1). Five-week-old rats were gavaged 5 days per week for 3 weeks with AFB 1 (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 AFB 1 pretreatment increased cell proliferation. Telomerase activity was decreased by DR and increased by the MD diet and AFB 1 pretreatment. The same trend was observed with GST-P + foci: in AFB 1-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.