The present study was designed to elucidate the inhibitory potential of Momordica charantia (Bitter Gourd) peel, pulp, seed and whole fruit extract on mouse skin papillomagensis with the modulatory influence of biotransformation system enzymes. Topical application of Momordica whole fruit extract (100 mu l/animal per day) during the peri-initiation stage (1 week before and 2 weeks after initiation) by 7,12-dimethylbenz[a]anthracene (DMBA) and/or during the tumor promotion stage reduced the (i) tumor burden to 4.26, 3.72 and 3.11 (positive control value: 5.42); (ii) cumulative number of papillomas to 81, 67 and 53 (positive control value: 103); and (iii) percent incidence of mice bearing papillomas to 100, 94 and 94, respectively (positive control value: 100). In a comparison of the anticarcinogenic efficacy of Momordica peel, pulp, seed and whole fruit extract (100 mu l/animal per day), after topical treatment during the peri-initiation and during the tumor promotion stage, revealed the modulation of the (i) tumor burden (tumors/mouse) to 3.06, 3.61, 3.17 and 3.11; (ii) cumulative number of papillomas to 49, 65, 54 and 53; and (iii) percent incidence of mice bearing papillomas to 84, 100, 94 and 94, respectively. Significant elevation in the sulfhydryl (-SH) level was observed in the liver and skin tissues by the topical treatment of Momordica peel, pulp, seed and whole fruit extract. Elevation in the hepatic levels of cytosolic glutathione S-transferase (GST) and microsomal cytochrome b(5) was also observed by the topical treatment of Momordica peel, seed and whole fruit extract. The results suggest the maximum chemopreventive potential is in the Momordica peel. Equivocal efficacy is in the Momordica seed and whole fruit extract. Biotransformation system enzymes may be the cause of this reduced papillomagenesis. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.