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Comparative Formation and Removal of Aflatoxin B₁-DNA Adducts in Cultured Mammalian Tracheal Epithelium¹

Graduate Programs in Toxicology and Molecular Biology, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah 84322-4620 [R. W. B., R. A. C.], and Department of Veterinary Pathology, University of California, Davis, California 95616 [D. W. W.]

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 µM 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. Labeled thymidine studies showed that cells of the tracheal epithelium did not turn over sufficiently to bias the apparent repair rates. These results demonstrated that carcinogen activation and repair capabilities of tracheal epithelium vary among species and that these processes likely relate to the presence of smooth endoplasmic reticulum containing non-ciliated tracheal epithelial cells in those species.

¹ Supported in part by National Institute of Environmental Health Sciences Grant R01 ES04813. Paper 3874 from the Utah Agricultural Experiment Station.

² To whom requests for reprints should be addressed.

Received 10/17/89. Revised 4/ 9/90.

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