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Pathobiological Effects of Acrolein in Cultured Human Bronchial Epithelial Cells¹

Department of Toxicology, Karolinska Institute, S-104 01 Stockholm, Sweden [R. C. G., J. M. D., K. S., C. E., L. A.] and Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892 [J. C. W., C. C. H.]

The ability of the highly reactive aldehyde acrolein to affect growth, membrane integrity, differentiation, and thiol status and to cause DNA damage has been studied at serum- and thiol-free conditions using cultured human bronchial epithelial cells. Acrolein markedly decreases colony survival at 3 µM whereas about 10-fold higher concentrations are required to increase membrane permeability, measured as uptake of trypan blue dye. Acrolein at micromolar concentrations also causes epithelial cells to undergo squamous differentiation as indicated by decreased clonal growth rate, dose-dependent increased formation of cross-linked envelopes, and increased cell planar surface area. Acrolein causes a marked and dose-dependent cellular depletion of total and specific free low-molecular-weight thiols as well as protein thiols. Exposure to acrolein did not cause oxidation of glutathione indicating that thiol depletion occurred by direct conjugation of reduced glutathione to acrolein without concomitant generation of active oxygen species. Furthermore, acrolein is genotoxic and causes both DNA single strand breaks and DNA protein cross-links in human bronchial epithelial cells. The results indicate that acrolein causes several cytopathic effects that relate to multistage carcinogenesis in the human bronchial epithelium.

¹ Supported in part by grants from the Health Effects Institute, the Workers Environment Health Fund, the Swedish National Board of Laboratory Animals, the Swedish Medical Research Council, the Swedish Cancer Society, and the Swedish Tobacco Company (R. C. G., J. M. D., K. S., C. E., and L. A.).

Research described in this article is conducted in part under contract to the Health Effects Institute, an organization jointly funded by the United States Environmental Protection Agency (Assistance Agreement X-812059) and automotive manufacturers. The contents of this article do not necessarily reflect the views of the Health Effects Institute, nor do they necessarily reflect the policies of the Environmental Protection Agency or automotive manufacturers.

² To whom requests for reprints should be addressed, at Department of Toxicology, Tomtebodavägen 30, Karolinska Institutet, S-104 01, Stockholm, Sweden.

Received 8/ 7/87. Revised 12/15/87. Accepted 12/30/87.

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