EFFECTS OF 1,4-PHENYLENEBIS(METHYLENE)SELENOCYANATE, PHENETHYL ISOTHIOCYANATE, INDOLE-3-CARBINOL, AND D-LIMONENE INDIVIDUALLY AND IN COMBINATION ON THE TUMORIGENICITY OF THE TOBACCO-SPECIFIC NITROSAMINE 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE IN A J MOUSE LUNG/

In this study we examined whether chemopreventive agents that had each been shown to be effective against lung tuorigenesis induced in A/J m ice by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were more effective when applied together as a ''cocktail'' than as individual c ompounds. Groups of A/J mice were fed a diet containing 1,4-phenyleneb is(methylene)selenocyanate (p-XSC; 5 ppm as selenium, 0.0005%), phenet hyl isothiocyanate (PEITC; 0.008%), indole-3-carbinol (I3C; 0.18%), d- limonene (d-L, 0.63%), or a mixture of all four at the above levels. M ice were fed experimental diets (AIN-76A plus a chemopreventive agent, or a mixture of the four chemopreventive agents) for 17 weeks. One we ek after beginning the experimental diets, the animals received a sing le i.p. injection of 10 mu mol NNK (2.07 mg) in 0.1 ml saline. Sixteen weeks after the NNK application the bioassay was terminated Dietary p -XSC, PEITC, I3C, d-L, and their admixture reduced significantly the n umber of lung tumors per mouse from 8.1 in the positive control to 3.2 , 3.7, 4.9, 2.4, and 2.5, respectively (p < 0.05). The inhibition of l ung tumor multiplicity in mice fed either the mixture or. d-L alone wa s also significantly stronger than in those fed the diet containing on ly I3C. However, neither individual agents nor their mixture had a mea surable effect on lung tumor incidence. Although the effect of the mix ture on lung tumor incidence in this assay remained imperfect, this pr eliminary investigation provides some basis for the future design of c hemoprevention studies.