The detection of DNA-protein cross-links in rat tracheal implants exposed in vivo to benzo[a]pyrene and formaldehyde.
The DNA damage associated with benzo(a)pyrene (B[a]P) and formaldehyde (HCHO) exposure in rat tracheal implants was determined by alkaline filter elution adapted to measure DNA-protein cross-links (DPC) in vivo. In addition, histopathological responses of the tracheal epithelium were quantitated after multiple exposures to 20 micrograms B[a]P and 0.2% HCHO. Compared to either agent alone, combined exposure for 1-4 weeks caused an increase in cellular atypia and greater thickness of hyperplastic and metaplastic lesions. HCHO exposure resulted in a dose-dependent increase in DPC with a maximal response of 85% DNA filter retention at 0.2% HCHO, which were mostly removed by 72 h. B[a]P did not cause DPC, but when tracheas were pre-exposed to 20 micrograms B[a]P followed by 0.05% HCHO there was a 15% decrease in HCHO-induced DPC. This competition between B[a]P and HCHO for sites presumably on DNA does not offer a clear explanation for their markedly enhanced cocarcinogenicity observed in previous studies, but does demonstrate the interaction between the two agents in tracheal epithelium.
Cosma
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GN
Biology Division, Oak Ridge National Laboratory, TN 37831.
Wilhite
A S
AS
Marchok
A C
AC
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004347:Drug Interactions; D005557:Formaldehyde / Q000633:toxicity*; D009092:Mucous Membrane / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D011506:Proteins; D005557:Formaldehyde; D001564:Benzo(a)pyrene; D004247:DNA