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.

[1]  J A Swenberg,et al.  Induction of squamous cell carcinomas of the rat nasal cavity by inhalation exposure to formaldehyde vapor. , 1980, Cancer research.

[2]  P. Nettesheim,et al.  Increased in vitro growth capacity of tracheal epithelium exposed in vivo to 7, 12-dimethylbenz(a)anthracene. , 1977, Cancer research.

[3]  J. Caton,et al.  Induction of preneoplastic and neoplastic lesions in grafted rat tracheas continuously exposed to benzo(a)pyrene. , 1977, Cancer research.

[4]  W. Baird,et al.  Benzo(a)pyrene:DNA adduct formation in early-passage Wistar rat embryo cell cultures: evidence for multiple pathways of activation of benzo(a)pyrene. , 1986, Cancer research.

[5]  D. Martin,et al.  Sequential appearance of anchorage independence, uncontrolled nuclear division and tumorigenicity in 7,12-dimethylbenz(a)anthracene-exposed rat tracheal epithelial cells. , 1987, Cancer research.

[6]  G. Cosma,et al.  The induction of growth-altered cell populations (tumor-initiation sites) in rat tracheal implants exposed to benzo[a]pyrene and formaldehyde. , 1987, Carcinogenesis.

[7]  P. Nettesheim,et al.  Tumor induction in tracheal grafts: a new experimental model for respiratory carcinogenesis studies. , 1974, Journal of the National Cancer Institute.

[8]  K. Kohn Assessment of DNA damage by filter elution assays. , 1986, Basic life sciences.

[9]  K. Kohn,et al.  Measurement of DNA damage in unlabeled mammalian cells analyzed by alkaline elution and a fluorometric DNA assay. , 1980, Analytical biochemistry.

[10]  G. Cosma,et al.  Benzo[a]pyrene- and formaldehyde-induced DNA damage and repair in rat tracheal epithelial cells. , 1988, Toxicology.

[11]  Andres J Klein-Szanto,et al.  An open-ended rat tracheal implant model: toxic effects of formaldehyde on the respiratory epithelium. , 1983, Toxicology letters.

[12]  D. Brutlag,et al.  Properties of formaldehyde-treated nucleohistone. , 1969, Biochemistry.

[13]  A. Marchok,et al.  Quantitation of growth-altered cell populations (tumor-initiation sites) induced in open-ended rat tracheal implants by split doses of benzo[a]pyrene. , 1987, Carcinogenesis.

[14]  W. Johnston,et al.  Progression-linked properties of specific-lesion cell populations from 7,12-dimethylbenz[a]anthracene-exposed rat tracheal implants. , 1986, Carcinogenesis.

[15]  P. Nettesheim,et al.  In vitro development of oncogenicity in cell lines established from tracheal epithelium preexposed in vivo to 7,12-dimethylbenz(a)anthracene. , 1978, Cancer research.

[16]  M. Casanova,et al.  Isotope effects and their implications for the covalent binding of inhaled [3H]- and [14C]formaldehyde in the rat nasal mucosa. , 1987, Toxicology and applied pharmacology.

[17]  Andres J Klein-Szanto,et al.  The effects of formaldehyde gas in a flow-through rat tracheal implant system. , 1984, Toxicology.

[18]  R. Jamasbi,et al.  Growth inhibition and DNA damage induced by benzo[a]pyrene and formaldehyde in primary cultures of rat tracheal epithelial cells. , 1988, Mutation research.

[19]  T. Starr,et al.  Differentiation between metabolic incorporation and covalent binding in the labeling of macromolecules in the rat nasal mucosa and bone marrow by inhaled [14C]- and [3H]formaldehyde. , 1984, Toxicology and applied pharmacology.

[20]  W. Dontenwill,et al.  Investigations on the effects of chronic cigarette-smoke inhalation in Syrian golden hamsters. , 1973, Journal of the National Cancer Institute.