Effect of frequency of isothiocyanate administration on inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced pulmonary adenoma formation in A/J mice

The abilities of phenethyl isothiocyanate (PEITC) and 6-phenylhexyl isothiocyanate (PHITC) to inhibit 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenicity, when administered by a standard four-dose protocol or by a single-dose protocol, were determined. Corn oil or isothiocyanates were administered once or for four consecutive days by gavage, with the final (or single) administration of corn oil or inhibitor occurring 2 h prior to a single i.p. injection of NNK (10 μmol/mouse). Sixteen weeks following NNK administration, the experiment was terminated and pulmonary adenomas were quantitated. Pretreatment with PEITC at a dose of 5 μmol or PHITC at a dose of 0.2 μmol resulted in significant reductions of tumor multiplicity compared to control, regardless of whether each isothiocyanate was administered once or four times. For both isothiocyanates, there were no statistically significant differences between dosing frequencies in inhibitory effects on tumor multiplicities and tumor incidences. Furthermore, the results achieved following a single pretreatment with either isothiocyanate were in good agreement with previous results obtained utilizing the four-dose protocol. Thus, it appears that most or all of the inhibitory potential of the four-dose protocol is due to the final dose of isothiocyanate.