Author

Hongwei Qian

Date of Graduation

1998

Document Type

Dissertation/Thesis

Abstract

The specific aims of the present investigation were to determine the genotoxicity and potential carcinogenicity of WFC of Type I and Type III roofing asphalt by using different genetic endpoints in mammalian cells in vitro and in rat in vivo. Morphological transformation studies in cultured BALB/c-3T3 cells indicated that at concentrations that allow less than 50% survival, neither of the WFC, with or without the hamster liver S9 activation system, significantly increased foci formation in BALB/c-3T3 cells. The conventional and immunofluorescent staining MN assays showed that both types of WFC caused a significant increase in the frequency of MNC and that 70% of MNC induced by WFC of roofing asphalt carried kinetochore-positive MN. A separate MN study with fractions of roofing asphalt WFC also indicated that the numbers of MNC in cultures treated with the WFC and fractions B, C, D, and E were significantly higher than those in the control culture, and that the slopes of the linear regressions for fractions B and C were greater than those for the WFC and fractions D and E. A clear dose-response of BNC also was induced by the WFC and fractions B and C. DNA adduct study in rat-lung-cell system showed that both WFCs caused DNA adduct formation in rat lung cells in a similar dose-related manner. Under the conditions studied, however, neither Type I nor Type III WFC induced DNA adducts in WBCs. This study, therefore, has demonstrated that although WFC from both types of roofing asphalt do not induce cell transformation in BALB/c-3T3 cells, these WFCs do have an ability to induce MN in vitro in V79 Chinese hamster lung cells. The damage appear to be due to spindle-fiber damage during cell division, in addition to chromosome breakages. The appearance of binucleated cells provided an additional evidence of numerical chromosomal aberrations. Fractions B and C are the most genotoxic components of roofing asphalt WFC. The covalent binding to target DNA in lung cells is integral to the genotoxicity of the roofing asphalt WFC.

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