Phenethyl isothiocyanate inhibits nitrosamine carcinogenesis in a model for study of oral cancer chemoprevention.
The anticarcinogenic effect of phenethyl isothiocyanate (PEITC) was examined in hamster buccal pouch mucosa exposed to N-nitrosomethylbenzylamine (NMBA). Unscheduled DNA synthesis (UDS) and induction of intraepithelial gamma-glutamyl transpeptidase (gamma-GT) histochemical foci were assessed as potential predictors of anticarcinogenicity. UDS mediated by in vitro exposure to NMBA (at 10 and 50 mM) was examined in mucosal samples derived following topical exposure of pouch mucosa to PEITC at concentrations of 0.5, 5, or 50 mM. In vivo PEITC pretreatment reduced NMBA-induced UDS in a dose dependent manner. PEITC treatment reduced induction of gamma-GT foci, detected in epithelial wholemounts derived over a period of 8-13 weeks of NMBA application, by an average of 96%. PEITC also reduced tumor formation by 94%. gamma-GT, in particular, may be a useful indicator for identification of effective oral cancer chemopreventive agents and combinations of agents.
Solt
Dennis B
DB
Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA. d-solt@northwestern.edu
Chang
Kuo wei
Kw
Helenowski
Irene
I
Rademaker
Alfred W
AW
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor; D006224:Cricetinae; D004261:DNA Replication / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009602:Nitrosamines / Q000633:toxicity; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D017879:Isothiocyanates; D009602:Nitrosamines; C058305:phenethyl isothiocyanate; D005723:gamma-Glutamyltransferase