This study examined the effects of
6-phenylhexyl isothiocyanate (
PHITC) on lung
tumorigenesis in F344 rats induced by the tobacco-specific
nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Two
biomarkers 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 quantified during the course of the
tumor induction experiment. Rats were 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 micromol/g NIH-07 diet, 60 rats; (3)
PHITC, 1 micromol/g NIH-07 diet, 20 rats; (4) control, 20 rats.
PHITC was added to the diet for 1 week prior to and during 111 weeks of NNK treatment. There were no effects of
PHITC on
body 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 of lung
tumors was 26% (P < 0.01 compared with NNK).
PHITC had no effect 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 bioassay than did those treated with NNK alone and significantly higher levels of NNAL plus
NNAL-Gluc excreted in urine at two time points during the bioassay. These results demonstrate that near lifetime administration of
PHITC to rats strongly inhibits the metabolic activation and lung tumorigenicity of NNK.