Inhibition of aflatoxin B1 mutagenesis in salmonella typhimurium and DNA damage in cultured rat and human tracheobronchial tissues by ellagic acid

Swapna Mandal, Arvind Ahuja, Narayan M. Shivapurkar, Shu Jun Cheng, John D. Groopman, Gary D. Stoner

Research output: Contribution to journalArticlepeer-review

Abstract

Ellagic acid (EA), a plant phenol found in various fruits and nuts, was examined for its ability to inhibit aflatoxin B1 (AFB1) mutagenesis in strain TA 100 of Salmonella typhimurium. In the presence of rat liver S-9 microsomal preparation, EA (1.5 μg/plate) inhibited the number of mutations induced by AFB, (0.5 μg/plate) by 50%. EA at a dose of 1000 μg/plate inhibited the mutation frequency by >90%. EA was also tested for its ability to inhibit the DNA binding and adduct formation of AFB1 in cultured explants of rat trachea and human tracheobronchus. Explants were incubated in medium containing EA at concentrations of 10, 50 and 100 μM for 16 h foUowed by the addition of 1 μM [3H]AFB1 and EA for 24 h. DNA was isolated by phenol extraction and hydroxylapatite chromatography. EA caused a dose-dependent inhibition in the covalent binding of AFB1 to the DNA of both the rat trachea (9-57% inhibition) and human tracheobronchus (24-79% inhibition). After acid hydrolysis of the isolated DNA, the AFB1-DNA adducts were separated by h.p.l.c. In tissues from both species, the major AFB1-DNA adducts were AFB1-N7-Gua [8,9-dihydro-8-(N7-guanyl)-9-hydroxyAFB1] and AFB1-N7-FaPyr (major) [8,9-dihydro-8- (2, 6-diamino-4-oxo-3,4-dihydro-pyrimid-5-yl formamido)-9-hydroxyAFB1], and the formation of these adducts was reduced by 28-76% in the presence of EA. These data indicate that EA has the potential to act as a naturally occurring inhibitor of AFB1-related respiratory damage in rats and in humans.

Original languageEnglish (US)
Pages (from-to)1651-1656
Number of pages6
JournalCarcinogenesis
Volume8
Issue number11
DOIs
StatePublished - Nov 1987
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research

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