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

Authors

R. Wayne Ball, Utah State University
Roger A. Coulombe Jr., Utah State UniversityFollow
Dennis W. Wilson, University of California - Davis

Document Type

Article

Journal/Book Title/Conference

Cancer Research

Volume

50

Issue

16

Publisher

American Association for Cancer Research

Publication Date

1990

First Page

4918

Last Page

4922

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 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.

Comments

Originally published by the American Association for Cancer Research. Publisher's PDF available through remote link.

Recommended Citation

Ball, R.W. and R.A. Coulombe, Jr. (1990). Comparative formation and removal of aflatoxin B1-DNA adducts in mammalian tracheal epithelium. Cancer Res. 50:4918-4922.