Aflatoxin-DNA adduct formation in chronically dosed rats fed a choline-deficient diet

Thomas F. Schrager, Paul M. Newberne, Anthony H. Pikul, John Davis Groopman

Research output: Contribution to journalArticle

Abstract

Nutritional modulation of male Fischer rats by a choline-deficient/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]AFB1 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 choline-deficient 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.

Original languageEnglish (US)
Pages (from-to)177-180
Number of pages4
JournalCarcinogenesis
Volume11
Issue number1
StatePublished - Jan 1990
Externally publishedYes

Fingerprint

Aflatoxins
Aflatoxin B1
DNA Adducts
Nutrition
Choline
Rats
Diet
Animals
Dose
Inbred F344 Rats
Tumor
DNA
Damage
Methionine
DNA Damage
Liver
High-performance Liquid Chromatography
Schedule
Modulation
Tumors

ASJC Scopus subject areas

  • Cancer Research
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology
  • Behavioral Neuroscience

Cite this

Aflatoxin-DNA adduct formation in chronically dosed rats fed a choline-deficient diet. / Schrager, Thomas F.; Newberne, Paul M.; Pikul, Anthony H.; Groopman, John Davis.

In: Carcinogenesis, Vol. 11, No. 1, 01.1990, p. 177-180.

Research output: Contribution to journalArticle

Schrager, TF, Newberne, PM, Pikul, AH & Groopman, JD 1990, 'Aflatoxin-DNA adduct formation in chronically dosed rats fed a choline-deficient diet', Carcinogenesis, vol. 11, no. 1, pp. 177-180.
Schrager, Thomas F. ; Newberne, Paul M. ; Pikul, Anthony H. ; Groopman, John Davis. / Aflatoxin-DNA adduct formation in chronically dosed rats fed a choline-deficient diet. In: Carcinogenesis. 1990 ; Vol. 11, No. 1. pp. 177-180.
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