Inhibitory effects of 6-phenylhexyl isothiocyanate on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolic activation and lung tumorigenesis in rats

Stephen S. Hecht, Neil Trushin, Jeffrey Rigotty, Steven G. Carmella, Anna Borukhova, Shobha Akerkar, Dhimant Desai, Shantu Amin, Abraham Rivenson

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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 μmol/g NIH-07 diet, 60 rats; (3) PHITC, 1 μmol/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.

Original languageEnglish (US)
Pages (from-to)2061-2067
Number of pages7
JournalCarcinogenesis
Volume17
Issue number9
DOIs
StatePublished - Sep 1996
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by National Cancer Institute Grant CA-46535. The bioassay was performed in the American Health Foundation Research Animal Facility, supported in part by National Cancer Institute Cancer Center Support Grant CA-17613. This grant also partially supports the Clinical Biochemistry Facility, which performed some of the analyses in this study, the Biostatistics and Computer Facility, which carried out the statistical evaluations, and the Organic Synthesis Facility, which provided the PHITC and NNK. We thank Rachid Hamid for preparing the diet, Chang-In Choi for supervising the bioassay and Brian Pittman and Edith Zang for statistical consultation.

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