Date of Graduation

1997

Document Type

Dissertation/Thesis

Abstract

The rat tracheal epithelial (RTE) cell transformation assays (by both in vitro and in vivo exposure) were used to study the potential pulmonary carcinogenesis of diesel emission particles (DEPs) and two diesel-related compounds, 1-nitropyrene (1-NP) and dibenzo(a,i)pyrene (DBP). An anchorage-independent growth and the tumorigenicity study in athymic nude mice were used to determine the neoplastic potential of the transformed RTE cell lines. Amplification of proto-oncogenes K-ras, c-jun, c-fos and c-myc was determined in the cell lines by differential polymerase chain reaction (PCR). Results from transformation assays show that DEPs and 1-NP induced RTE cell transformation only via in vivo exposure, whereas, DBP induced RTE cell transformation via both in vitro and in vivo exposures. The fraction of transformed foci becoming cell lines is in the order: 1-NP (25/48) {dollar}>{dollar} DBP (8/28) {dollar}>{dollar} DEPs (0/30). Results of neoplastic potential studies showed: (1) 3 of 5 cell lines from DBP- and 5 of 5 from 1-NP-induced transformed foci displayed anchorage-independent growth; (2) 2 of 5 DBP-induced and all five 1-NP-induced cell lines produced squamous cell carcinoma (SCC) in nude mice. Results from amplification studies of proto-oncogenes indicate that there are no significant differences among the cell lines induced by different agents. In summary, conclusions from this study are: (1) diesel emission particles and the two related chemicals are capable of inducing cell transformation in RTE cells, however, the transforming activity of DEPs and 1-NP may depend on the type of exposure and metabolic activation; (2) since none of the transformed foci induced by DEPs and only fractions of the transformed foci induced by 1-NP and DBP can become cell lines, some of the morphological changes of RTE cells are non-genetic; (3) transformed RTE cell lines induced by 1-NP may possess stronger neoplastic potential than those induced by DBP; (4) amplification of c-jun and K-ras may be, in part, related to RTE cell transformation and immortality.

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