PMID: 2116221Aug 15, 1990Paper

Comparative formation and removal of aflatoxin B1-DNA adducts in cultured mammalian tracheal epithelium

Cancer Research
R W BallR A Coulombe

Abstract

Aflatoxin B1 (AFB1) DNA binding, adduct formation, and AFB1-DNA adduct repair were studied in tracheal explants from rabbit, hamster, and rat. These species vary in populations of cytochrome P-450-containing nonciliated tracheal epithelial cells. Explants were cultured in media containing 0.5 microM AFB1 for 12 h. After the 12-h treatment, the explants were cultured for time intervals up to 84 h and then analyzed for AFB1-DNA adducts. Binding of AFB1 to DNA was highest in rabbit tracheal explants (78 pmol/mg DNA), followed by the hamster (28 pmol/mg DNA), with the rat (3 pmol/mg DNA) showing minimal AFB1-DNA binding. Repair rates in the hamster and rat were constant over time with removal of the 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 accounting for the majority of adduct disappearance. The rabbit demonstrated biphasic repair of adducts; all adduct types [8,9-dihydro-8-(2-amino-6-formamido-4-oxo-3,4-dihydropyrimid-5- ylamino)-9- hydroxyaflatoxin B1] were rapidly removed during the first 12 h posttreatment with AFB1, followed by a slower removal phase of primarily 8,9-dihydro-8-N7-guanyl)-9-hydroxyaflatoxin B1. After 84 h, 90, 72, and 55% of the initial adducts were removed in the rabbit, hamster, and rat, respectively. ...Continue Reading

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