Date of Award

12-1996

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Environmental Science

First Advisor

Dr. M.S.A. Nur-E-Kamal

Second Advisor

Ibrahim M. Ibrahim

Third Advisor

Dr. Gamal Abdul-Aal

Abstract

The carcinogenic potential of benzo[α]pyrene (B(α)P) and dimethylbenzanthracene (DMBA) was tested using mouse leukemic cell lines L-5178 R and S types in tissue culture condition. It was found that B(α)P and DMBA inhibited the synthesis of DNA of R and S types of cells to about 34%, at 10 mM concentration. While B(α)P and DMBA did not show any acute toxic effect on mouse cell line Rand S types at 1 mM concentration separately. Both R and S types of cells were allowed to grow for several days in the presence of 1 mM DMBA and B(α)P respectively. Several independent clones were isolated from both DMBA and B(α)P treated cells and cultured separately. The effect of DMBA and B(α)P on changing the structure of DNA (in relation to their growth and oncogenicity) was then checked in these clones. It was found that several clones have changed their growth pattern showing a shorter generation time. By soft agarose colony formation assay, the oncogenic behavior of B(α)P and DMBA treated clones was determined. It was found that 25% of the clones have changed (15% increase and 10% decrease) their oncogenic behavior. This suggests that B(α)P and DMBA caused some permanent changes (most likely DNA) in the cell. Attempts were made to characterize these changes at the molecular level by analyzing expression of Glutathione-S-transferase (GST) and Ras GTPase by immunoblotting. There was no significant change in the expression level of GST and Ras protein. Mutation in p53 gene exons 6 ,8, and 9 was also checked by polymerase chain reaction (PCR). No large scale mutation was found in exons 6,8, and 9 of p53 gene. This investigation suggests that both B(α)P and DMBA have the ability to change structure of DNA leading to increased carcinogenicity in tissue culture condition. This study has provided an additional support, using in vitro cell culture techniques to show the increased risk of cancer due to the exposure to B(α)P and/or DMBA present as environmental pollutant.

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