TY - JOUR
T1 - Aflatoxin-dna adduct formation in chronically dosed rats fed a choline-deficient diet
AU - F.schrager, Thomas
AU - M.newberne, Paul
AU - H.pikul, Anthony
AU - D.groopman, John
N1 - Funding Information:
The authors gratefully acknowledge the critical comments and review of this research by Dr Adrianne Rogers. This research supported in part by PHS grant CA 46288-01.
PY - 1990/1
Y1 - 1990/1
N2 - Nutritional modulation of male Fischer rats by a cholinedeficient/methionine-low diet dramatically increases hepatocarcinogenesis and reduces time to first tumors induced by aflatoxin B1 (AFB1) The effect of this diet on hepatic aflatoxin-DNA adduct burden in male Fischer rats dosed with a carcinogenic regimen of AFB1 was examined in this study. After 3 weeks of ingestion of a choline-deficient/ methionine-low diet or control semi-purified diet, rats were administered a carcinogenic regimen of 25 μg [3H]AFB3 for 5 days a week over 2 weeks. Six choline-deficient and four control diet rats were killed 2 h after each dose, and liver DNA isolated. In addition, hepatic DNA was isolated from animals 1, 2, 3, and 11 days after the last [3H]AFB1 administration. At all time points HPLC analysis of aflatoxin-DNA adducts was performed to confirm radiometric determinations of DNA binding levels. No significant quantitative differences in AFB1-DNA adduct formation between the dietary groups were observed following the first exposure to [3H]AFB1; however, total aflatoxin-DNA adduct levels in the cholinedeficient animals were significantly increased during the multiple dose schedule. When total aflatoxin-DNA adduct levels were integrated over the 10 day dose period, a 41% increase in adduct burden was determined for the cholinedeficient animals. While this increase in DNA damage is consistent with the hypothesis that DNA damage is related to tumor outcome, the biochemical basis for this effect still needs to be elucidated.
AB - Nutritional modulation of male Fischer rats by a cholinedeficient/methionine-low diet dramatically increases hepatocarcinogenesis and reduces time to first tumors induced by aflatoxin B1 (AFB1) The effect of this diet on hepatic aflatoxin-DNA adduct burden in male Fischer rats dosed with a carcinogenic regimen of AFB1 was examined in this study. After 3 weeks of ingestion of a choline-deficient/ methionine-low diet or control semi-purified diet, rats were administered a carcinogenic regimen of 25 μg [3H]AFB3 for 5 days a week over 2 weeks. Six choline-deficient and four control diet rats were killed 2 h after each dose, and liver DNA isolated. In addition, hepatic DNA was isolated from animals 1, 2, 3, and 11 days after the last [3H]AFB1 administration. At all time points HPLC analysis of aflatoxin-DNA adducts was performed to confirm radiometric determinations of DNA binding levels. No significant quantitative differences in AFB1-DNA adduct formation between the dietary groups were observed following the first exposure to [3H]AFB1; however, total aflatoxin-DNA adduct levels in the cholinedeficient animals were significantly increased during the multiple dose schedule. When total aflatoxin-DNA adduct levels were integrated over the 10 day dose period, a 41% increase in adduct burden was determined for the cholinedeficient animals. While this increase in DNA damage is consistent with the hypothesis that DNA damage is related to tumor outcome, the biochemical basis for this effect still needs to be elucidated.
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U2 - 10.1093/carcin/11.1.177
DO - 10.1093/carcin/11.1.177
M3 - Article
C2 - 2104783
AN - SCOPUS:0025141571
SN - 0143-3334
VL - 11
SP - 177
EP - 180
JO - Carcinogenesis
JF - Carcinogenesis
IS - 1
ER -