CHEMOPREVENTIVE EFFECTS OF 3-PHENYLPROPYL ISOTHIOCYANATE ON HAMSTER LUNG TUMORIGENESIS INITIATED WITH N-NITROSOBIS(2-OXOPROPYL) AMINE

The chemopreventive effects of 3-phenylpropyl isothiocyanate (PPITC) w ere investigated in N-nitrosobis(2-oxopropyl)amine (BOP)-initiated ham sters. A total of 120 female 5-week-old hamsters were divided into 6 g roups. Animals in groups 1-3, each consisting of 30 hamsters, were twi ce sc injected 7 days apart as an initiation treatment. Hamsters in gr oups 1 and 2 were respectively given 100 mu mol and 10 mu mol of PPITC by gavage 2 h prior to each BOP treatment. Animals in group 3 were tr eated with BOP alone, serving as an initiation-positive control. Anima ls in groups 4-6, each consisting of 10 hamsters, were given 100 mu mo l or 10 mu mol of PPITC alone, or non-treated, thus being available as matched negative controls to groups 1-3. At termination (experimental week 51 after the first BOP injection), the incidences of lung adenom as and/or adenocarcinomas were significantly decreased in groups 1 and 2 as compared to the group 3 value (P < 0.01). The combined lung tumo r incidences were inhibited by 94% and 59% at 100 and 10 mu mol doses, respectively. The inhibitory effects of PPITC were thus dose-dependen t. The data for multiplicity of lung tumors dramatically illustrated t he inhibitory effects of PPITC, and there were also statistically sign ificant differences in the chemopreventive effect between 100 mu mol a nd 10 mu mol PPITC treatments. On the other hand, the PPITC treatments did not significantly modulate the development of neoplastic lesions in the pancreas, liver and kidney, although the treatments did show in hibitory tendencies, except on the liver lesions. Under the present ex perimental conditions, PPITC itself did not exhibit tumorigenicity or apparent toxicity. The results in the present study thus clearly indic ate that PPITC has an effective chemopreventive action on BOP-induced lung tumorigenesis in hamsters.