Date of Award

12-1997

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Environmental Science

First Advisor

Prof. Nawal Abd EI-Hay Ahmed

Second Advisor

Fazal K. Dar

Third Advisor

Dr. Rafie Hammoud Alwash

Abstract

The cytotoxic effect of methomyl carbamate was studied in three groups (control group, 1 % treated group and 10% treated group) and each group contain 2-3 White Wistar rats. The 1% treated group was received 1 % of methomyl LD50, while the 10% treated group was received 10% of methomyl LD50. The administration was orally and repeated three times with 24 hr intervals time. The effect of methomyl was investigated in four experimental run, by analysing the change in cell count in bone marrow after methomyl treatment. It was found that methomyl treatment caused significant reduction in cell number in rat bone marrow indicating that methomyl inhibits cell division. The molecular mechanism of inhibition of cell division was investigated. Analysis of DNA in treated and control animals showed that DNA synthesis is not inhibited upon methomyl treatment. Further investigation of gene products of Ras growth signaling pathway showed that methomyl treatment inhibited the expression of genes that are considered as primary response element (eg. C-Fos) of activation of Ras growth signal transduction pathway. These results indicate that methomyl treatment inhibits cell division by inhibiting, at least partly, Ras-mediated growth signaling pathway. In addition, cytotoxic effect of carbamate on rat was studied by analyzing the expression of two key molecules, cytochrome P-450 and GST proteins which are considered as markers of toxic effect. It was found that cytochrome P-450 gene expression was induced significantly after methomyl treatment while GST level did not change significantly. This suggests that methomyl is a mild toxic agent for mammals and cytochrome P-450 is involved in its metabolism. It might be advisable to use methomyl as insecticide under special precautions.

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