Chemopreventive effects of 3-phenylpropyl isothiocyanate on hamster lung tumorigenesis initiated with N-nitrosobis(2-oxopropyl)amine.

Abstract

The chemopreventive effects of 3‐phenylpropyl isothiocyanate (PPITC) were investigated in N‐nitrosobis(2‐oxopropyl)amine (BOP)‐initiated hamsters. A total of 120 female 5‐week‐old hamsters were divided into 6 groups. Animals in groups 1–3, each consisting of 30 hamsters, were twice sc injected 7 days apart as an initiation treatment. Hamsters in groups 1 and 2 were respectively given 100 μmol and 10 μmol of PPITC by gavage 2 h prior to each BOP treatment. Animals in group 3 were treated with BOP alone, serving as an initiation‐positive control. Animals in groups 4–6, each consisting of 10 hamsters, were given 100 μmol or 10 μmol 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 adenomas and/or adenocarcinomas were significantly decreased in groups 1 and 2 as compared to the group 3 value (P<0.01). The combined lung tumor incidences were inhibited by 94% and 59% at 100 and 10 μmol doses, respectively. The inhibitory effects of PPITC were thus dose‐dependent. The data for multiplicity of lung tumors dramatically illustrated the inhibitory effects of PPITC, and there were also statistically significant differences in the chemopreventive effect between 100 μmol and 10 μmol 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 inhibitory tendencies, except on the liver lesions. Under the present experimental conditions, PPITC itself did not exhibit tumorigenicity or apparent toxicity. The results in the present study thus clearly indicate that PPITC has an effective chemopreventive action on BOP‐induced lung tumorigenesis in hamsters.