Metabolism of Carcinogenic Nitrosamines by Rat Nasal Mucosa and the Effect of Diallyl Sulfide

Jun Yan Hong, Theresa Smith, Mao Jung Lee, Weisheng Li, Bing Li Ma, Shu M. Ning, John F. Brady, Paul K. Thomas, Chung S. Yang

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72 Scopus citations

Abstract

Kai nasal cavity is one of the target organs for carcinogencsis inducedby. V-nitrosodimethylamine (N'DMA),. V-nitrosodiethylamine (NDKA),and 4-(mcthylnitrosamino)-l-(3-pyridyl)-l-butanone(NNK). The presentwork investigated the metabolism of these nitrosamines by rat nasalmicrosomes. as »ellas the possible modulating factors. Microsomesprepared from rat nasal mucosa «ereefficient in metabolizing thesenitrosamines. In general, the metabolism of the nitrosamines »asslightlyhigher in 9-week-old rats than in 4-wcck-old animals, and there »asnosex-related difference. Fasting of rats for 48 h, which is known to inducehepatic cytochrome P45UIIKI and N'DMA metabolism, did not increasethe nasal metabolism of NDMA, NDKA, or NNK. Pretreatment of ratswith acetone, another inducer of hepatic P450IIKI, did not increase themetabolism of NDMA. Furthermore, it decreased the nasal metabolismof NDKA and NNK. Immunoinhibition studies suggest that, in the nasalmucosa, P450IIK1 is only partially responsible for the oxidation ofNDMA and other P45Ãoeisozymes are responsible for the metabolism ofNDEA. A single p.o. pretreatment of male rats with diallyl sulfide(DAS),a component of garlic oil. caused a significant decrease in the oxidativemetabolism of NDKA and NNK in rat nasal mucosa. Whereas the nasalmetabolism of NDMA was reduced by DAS pretreatmcnt, there »asnochange in the amount of the nasal microsomal proteins immunoreactivewith the antibodies against P450IIE1. The inhibitory effect of DAS onthe nasal oxidatnc metabolism of NDMA, NDKA, and NNK »asalsoobserved in experiments in vitro. The results demonstrate the ability ofnasal mucosa to metabolically activate these nitrosamines and the inhibition of this process by DAS, suggesting that DAS may be effective ininhibiting the related nasal tumorigenesis.

Original languageEnglish (US)
Pages (from-to)1509-1514
Number of pages6
JournalCancer Research
Volume51
Issue number5
StatePublished - Mar 1991

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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