Rapid induction of gamma-glutamyl transpeptidase-rich intraepithelial clones in 7,12-dimethylbenz(a)anthracene-treated hamster buccal pouch

Abstract

Individual gamma-glutamyl transpeptidase (GGT)-stained cells and cell doublets were rapidly induced in the epithelium of hamster buccal pouch treated with biweekly topical applications of 0.5%, 7,12-dimethylbenz(a)anthracene (DMBA) in mineral oil. The cells were detected histochemically in whole mounts of pouch epithelium harvested as early as 3 days after the first application of this carcinogen. During 3 consecutive weeks of DMBA treatment, progressively larger GGT-stained epithelial cell populations (plaques) up to 0.5 mm in diameter were encountered. Similar GGT-stained lesions were not detected in whole mounts of untreated epithelium and were rarely seen in GGT-stained whole mounts prepared from mineral oil-treated pouch epithelium. In an experiment designed to assess the stability of the GGT-staining pattern, very few plaques could be detected 12 weeks after a 3-week regimen of six DMBA applications. However, data are presented suggesting that a brief series of three DMBA applications reinduced GGT histochemical activity in occult intraepithelial plaques, which had los enzyme activity but had persisted over an 11-week treatment-free interval. The clonal nature of the GGT-stained plaques for their apparent ability to persist in an occult form for several weeks or months lend further support to the hypothesis that these carcinogen-altered cell populations may be potential precursors for the development of squamous epithelial neoplasia.