Comparative histochemical investigation of the glutathione S-transferase placental form and γ-glutamyltranspeptidase during N-nitrosobis(2-hydroxypropyl)amine-induced lung carcinogenesis in rats

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Abstract
Immunohistochemical staining using anti-rat glutathione S-transferase placental form (GST-P) rabbit antibody and enzyme histochemical staining for γ-glutamyltranspeptidase (γ-GT) were investigated in lesions appearing during lung carcinogenesis induced by N -nitrosobis(2-hydroxypropyl)amine (BHP) in rats. Rats were given BHP at a concentration of 2000 p.p.m. in drinking water, and were killed after 12 weeks of BHP intake, after 12 weeks of BHP intake followed by 12 weeks of tap water intake or after 20 weeks of continuous BHP intake. It was found that bronchiolo-alveolar hyperplasias, adenomas, adenocarcinomas, squamous metaplasias and squamous cell carcinomas had been induced by BHP. All of the squamous metaplasias and squamous cell carcinomas were shown to stain with GST-P but not with γ-GT. On the other hand, the hyperplasias, adenomas and adenocarcinomas stained with γ-GT to various degrees and in different areas, but did not stain with GST-P. The incidence of γ-GT phenotype and the average percentage of γ-GT positive areas in hyperplasias and adenomas suggested that adenocarcinomas might develop from hyperplasias and adenomas. These results suggest that GST-P is a marker for squamous lesions while γ-GT is a marker for adenomatous lesionsin rat lung carcinogenesis. Furthermore, squamous metaplasias appear to be preneoplastic lesions of squamous cell carcinomas while γ-GT-positive hyperplasias or adenomas are preneoplastic lesions of peripheral adenocarcinomas.