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

The effects of methyl-deficiency and dietary restriction (DR) on hepatic ce ll proliferation and telomerase activity was studied in male Fischer 344 ra ts pretreated with aflatoxin B-1 (AFB(1)). Five-week-old rats were gavaged 5 days per week for 3 weeks with AFB(1) (25 mug/rat per day) or solvent (10 0 mul 75% dimethylsulfoxide). Rats were then divided into four groups. Two groups were fed a methyl-sufficient (MS) diet either ab libitum (AL) or wit h 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, tel omerase activity. and the number of glutathione S-transferase-P positive (G ST-P+) foci were determined. DR reduced hepatic cell proliferation, while t he MD diet and AFB(1) pretreatment increased cell proliferation. Telomerase activity was decreased by DR and increased by the MD diet and AFB(1) pretr eatment. The same trend was observed with GST-P+ foci: in AFB(1)-pretreated rats, methyl deficiency increased the number of foci, while DR decreased t he number. These results are consistent with a role of telomerase in hepato carcinogenesis. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.