INHIBITORY EFFECTS OF 6-PHENYLHEXYL ISOTHIOCYANATE ON 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE METABOLIC-ACTIVATION AND LUNG TUMORIGENESIS IN RATS

This study examined the effects of 6-phenylhexyl isothiocyanate (PHITC ) on lung tumorigenesis in F344 rats induced by the tobacco-specific n itrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), Two b iomarkers of NNK metabolism, 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)- releasing hemoglobin adducts and 4-(methylnitrosamino)-1-(3-pyridyl)-1 -butanol (NNAL) and its glucuronide (NNAL-Gluc) in urine, were also qu antified during the course of the tumor induction experiment. Rats wer e divided into groups as follows: (1) NNK, 2 p.p.m. in drinking water, 60 rats; (2) NNK, 2 p.p.m. in drinking water and PHITC, 1 mu mol/g NI H-07 diet, 60 rats; (3) PHITC, 1 mu mol/g NIH-07 diet, 20 rats; (4) co ntrol, 20 rats. PHITC was added to the diet for 1 week prior to and du ring 111 weeks of NNK treatment, There were no effects of PHITC on bod y weight, mortality, blood chemistry or hematology, Seventy percent of the rats treated with NNK had adenoma or adenocarcinoma of the lung, In the rats treated with NNK plus PHITC, the total percent incidence o f lung tumors was 26% (P < 0.01 compared with NNK), PHITC had no effec t on the total incidence of exocrine pancreatic tumors induced by NNK, The rats treated with PHITC and NNK had significantly lower levels of HPB-releasing hemoglobin adducts throughout the course of the bioassa y than did those treated with NNK alone and significantly higher level s of NNAL plus NNAL-Gluc excreted in urine at two time points during t he bioassay. These results demonstrate that near lifetime administrati on of PHITC to rats strongly inhibits the metabolic activation and lun g tumorigenicity of NNK.