These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Inhibition of methyl-n-amylnitrosamine hydroxylation by diallyl sulfide and phenethylisothiocyanate in the rat.
    Author: Morris CR, Chen SC, Hinman C, Mirvish SS.
    Journal: Nutr Cancer; 2000; 37(2):199-206. PubMed ID: 11142094.
    Abstract:
    Formation of the stable 2-, 3-, and 4-hydroxy derivatives of methyl-n-amylnitrosamine (MNAN) probably reflects cytochrome P-450-catalyzed activation of MNAN by 1-hydroxylation. Here we studied inhibition of the oxidation of MNAN to hydroxy-MNANs (HO-MNANs) by freshly excised tissues from MRC-Wistar rats treated with the vegetable-derived chemicals diallyl sulfide (DAS) and phenethylisothiocyanate (PEITC). Rats were gavaged with DAS (200 mg/kg), PEITC (163 mg/kg), or vehicle (corn oil) alone. After various times, the rats were killed, the esophagus, nasal mucosa, and liver were removed, and the tissues/tissue slices were incubated for two hours with 23 microM MNAN. HO-MNAN formation was measured by gas chromatography-thermal energy analysis. Significant (p < 0.01) 72-75%, 40%, and 44% inhibitions of total HO-MNAN formation were observed for nasal mucosa removed at 3-18 hours, for esophagus at 18 hours, and for liver at 3 hours, respectively, after gavage of DAS. Significant (p < 0.03) 46-75% inhibition of HO-MNAN formations was observed for the esophagus at 2-24 hours after gavage of PEITC. In disposition studies, rats were treated with DAS (200 mg/kg) in corn oil and sacrificed after various intervals. DAS was determined by gas chromatography of tissue homogenate extracts. After gavage of DAS, its total recovery from all tissues studied was 27% of the dose after 45 minutes and 15-19% after 90 and 180 minutes, with > 80% of the recovered DAS in the stomach contents. Up to 2% per tissue of the recovered DAS was found in the stomach wall, liver, and blood. After intraperitoneal injection of DAS, < or = 2% of the dose was recovered in the blood and < or = 0.7% in the liver. Hence, gavage of DAS and PEITC significantly inhibited HO-MNAN formation for up to 18 and 24 hours, respectively, whereas DAS was > 80% metabolized 90 minutes after its gavage. These findings suggest that long-lasting inhibitors or their metabolites, or inactivation of P-450 enzymes, were responsible for the persistence of inhibition of MNAN metabolism.
    [Abstract] [Full Text] [Related] [New Search]