PMID: 9659577Jul 11, 1998Paper

Immunohistochemical detection of CYP2E1 and 2-S-glutathionyl acetate in murine lung tumors: diminished formation of reactive intermediates of 1,1-dichloroethylene

Experimental Lung Research
P G Forkert

Abstract

This study investigates the potential of urethane-induced lung tumors to activate 1,1-dichloroethylene (DCE), a chemical that causes Clara cell damage in mice. Metabolism of DCE is catalyzed by the cytochrome P450 isozyme CYP2E1 to the DCE-epoxide, as assessed by formation of 2-S-glutathionyl acetate (GTA), the glutathione (GSH)-conjugated product of the epoxide. Immunohistochemical studies were performed in normal non-tumor- and tumor-bearing mice to determine lung cells that contained CYP2E1 available for DCE metabolism. The site of GTA formation was also determined. The results showed that most of the CYP2E1 were expressed in Clara cells from normal lung and in uninvolved tissue of tumor-bearing lung. In contrast, CYP2E1 was minimally expressed in neoplastic tissue, including hyperplasias, adenomas, and carcinomas. Parallel studies of adjacent lung sections revealed that GTA immunostaining was most intense in Clara cells of normal lung tissue and in uninvolved tissue of tumor-bearing lungs from DCE-treated mice. However, GTA staining was negligible at all tumor sites. These results demonstrated that the cellular sites where CYP2E1 was expressed were the same as those in which the GTA metabolite was identified. They further s...Continue Reading

References

Jun 1, 1991·Environmental Health Perspectives·A M Malkinson
Jul 1, 1987·Canadian Journal of Physiology and Pharmacology·P G ForkertW J Racz
Feb 1, 1986·Canadian Journal of Physiology and Pharmacology·P G ForkertK M Troughton
Feb 1, 1982·Experimental Lung Research·P G Forkert, E S Reynolds
Apr 14, 1995·Chemico-biological Interactions·T F DowsleyJ L Bolton

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Citations

Jan 7, 2000·The American Journal of Pathology·R J MasonJ M Shannon

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