| Summary: | 碩士 === 中國醫藥學院 === 醫學研究所 === 89 === The first step in the initiation process of arylmine carcinogen induced carcinogenesis involves metabolic activation of these carcinogens to reactive intermediate, that are capable of binding to target tissue macromolecules such as DNA. N-acetylation is a major metabolic pathway for arylamine carcinogens which is catalyzed by host cytosolic N-acetyltransferase (NAT), using acetyl coenzyme A as a cofactor. Arylamine, such as 2-aminofluorene (2-AF), are N-acetylated to become 2-acetylaminofluorene, and can undergo further activation or detoxification reations. NAT activity in human and several animal species are genetically determined, and the rapid NAT2 phenotype has been shown to predispose humans to colorectal and breast cancer, whereas the rapid NAT1 and slow NAT2 phenotype are related to arylamine-induced bladder cancer.
In this study, Indole-3-acetic acid methyl ester (IAA-Me) was used to determine the cell growth in human bladder cancer cell line (T-24 and TSGH 8301) and inhibition of arylamine NAT activity and Sprague-Dawley (SD) rats’ tissue, and to detect the 2-AF metabolism in SD rat. The results demonstrated that cytotoxicity, DNA damage, morphological change, the inhibition of S phase in cell cycle and intracellular cyclins in T-24 and TSGH 8301 were resulted by IAA-Me, and also in a dose-dependent mannar. And the results demonstrated that NAT activity in intact cells of lymphocytes from normal SD rat’s WBC and T-24 were promoted by IAA-Me because of high extracellular NAT level by cell membrane rupture, but not NAT mRNA levels, sequence mutation, intracellular NAT levels. NAT activity were inhibited in normal SD rat’s tissues (liver, blood, bladder, colon, kidney) and T-24 cytosols by IAA-Me, and the effects also resulted in a dose-dependent mannar. Dietary treatment with Me-IAA to the rat indicate that IAA-Me can affect metabolism of 2-AF and distribution of 2-AF metabolites in SD rat’s different tissues.
|
|---|
