Placental glutathione S-transferase isoenzyme expression during promotion of two-stage hamster cheek-pouch carcinogenesis.

Glutathione S-transferases (GSTs) are the products of a multigene family. A well-established function of GSTs is to metabolize carcinogens by catalysing the conjugation of electrophilic substrates to glutathione. Whether placental GST (GST-P) is expressed during the promotion of two-stage hamster buccal-pouch mucosa (HBPM) carcinogenesis was investigated here, using 7,12-dimethylbenz[a]anthracene (DMBA) as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. Cytoplasmic and nuclear staining for GST-P was seen in pouches treated with DMBA for 4 or 16 weeks, as well as in those treated with DMBA for 4 weeks and then TPA for 12 weeks. No GST-P positivity was seen in any pouches treated with only TPA or with mineral oil for either 4 or 16 weeks. The average number of GST-P-stained foci in the groups treated with DMBA for 16 weeks (246 +/- 96; mean +/- SD) or DMBA for 4 weeks followed by TPA for 12 weeks (186 +/- 67) was significantly higher than in pouches treated with only DMBA for 4 weeks (97 +/- 24). These results demonstrate that TPA alone is not sufficient for GST-P expression in hamster buccal pouch mucosa. However, after being initiated with DMBA, then promoted with TPA, GST-P activity is induced in hamster buccal pouch mucosa during squamous-cell carcinogenesis. This underpins the suggestion that GST-P may play an important part during the promotion stage of oral carcinogenesis.