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KMID : 0385019960120010061
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Korean Journal of Laboratory Animal Science
1996 Volume.12 No. 1 p.61 ~ p.67
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Metabolic Activation of 2-Acetylaminofluorene is Required for Expression of Dioxin Receptor Mediated Cytochrome P4501A1/2 in Hepatocarcinogenesis
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이철호/Lee, Chul Ho
현병화/최양규/정규식/윤원기/윤종주/민병길/Hyun, Byung Hwa/Choi, Yang Kyu/Jeong, Kyu Shik/Yoon, Won Kee/Yoon, Zong Zhu/Mheen, Byoung Gil
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Abstract
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The expression levels and regional expressions of eytochrome P1501A1/2(CYPIA1/2) on F344 rat with treatments of diethylnitrosamine (DEN), partial hepatectomy (PH) and 2-acetylaminofluorene(2-AAF) was studied using immunohistochemical study. From 2 weeks until 8 weeks after intraperitoneal injection of UFN 12(㎎/㎏), group I (n=6) as a control w-a, given a basal diet after administration of saline instead of DEN and group II (n=9) was given 0.004% in basal diet after administration of DEN as an experimental group. Both groups were subjected to two thirds PH at 3 weeks after DEN or saline injection and then killed and fixed in 4% paraformal dehyde for paraffin embedded liver sections by studying of immuoreactivity of eytochrome P450 at week 8. AAF exposure for 8 weeks caused significant induction of the number (No./㎠) and areatmm/㎠) of GST p positive liver foci, a marker for single initiated cells and preneoplastic foci compared to untreated group. The average size of most types of foci was increased during continued AAF exposure of 8 weeks. Immunostaining of eytochrome P4501A1/2 from ensecutive thin sections from control and AAF treated liver revealed that hepatic CYP1A1/2 expression predominantly- expressed in periportal hepatocytes. N-hydroxylation, and obligators initial steep in the activation of 2-AAF into electrophilic DNA binding metabolites is catalyzed predominantly be cytoehrome P4501A1/2 enhanced protein aimed to protect the cell from further damage at the area of periportral hepatocytes. Differential localization of hepatocytes indicated that this regional selectivity is demonstrated heterogeneity of CYP1A1/2 expression and variation in expression may be of significance in assessing cell specific toxicities of various drugs and carcinogens.
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KEYWORD
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