Interactive effects of methyl-deficiency and dietary restriction on 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 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 microg/rat per day) or solvent (100 microl 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.
Chou
M W
MW
Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson AR 72079, USA. mchou@nctr.fda.gov
Mikhailova
M V
MV
Nichols
J
J
Poirier
L A
LA
Warbritton
A
A
Beland
F A
FA
D016604:Aflatoxin B1 / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002455:Cell Division; D002796:Choline Deficiency / Q000150:complications*; D005508:Food Deprivation; D008099:Liver / Q000201:enzymology* / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D008297:Male; D009752:Nutritional Status; D011230:Precancerous Conditions / Q000201:enzymology / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D019098:Telomerase / Q000378:metabolism*
D002273:Carcinogens; D016604:Aflatoxin B1; D019098:Telomerase