Prevention of genotoxicity by polyphenol acetates mediated by a novel membrane-bound transacetylase

G. Gupta1, E. Kohli1, V. Rohil1, R. Kumari1, H. G. Raj1, V. S. Parmar2, Y. K. Tyagi1, G. Pal1, A. Kumar1, S. C. Jain2 and C. E. Olsen3

1 V. P. Chest Institute and 2 Deptartment of Chemistry, Univ. of Delhi, Delhi, India;3 Chemistry Department Royal Vetrinary & Agricultural University Copenhagen, Denmark

AIM: A large number of polyphenolic compounds have exhibited potency to inhibit mutagenicity and carcinogenicity in animal model and cell cultures. Our earlier work revealed the remarkable ability of acetoxy-4- methyl coumarins in the prevention of aflatoxin B1(AFB1) induced genotoxicity in bone marrow and lung cells. We have in this presentation extended the observations to the action of other polyphenol acetates such as the acetoxy derivatives of quercetin, ellagic acid and xanthone. METHODS: The transacetylase enzyme inhibition was assayed with respect to the test compounds that were to be analyzed. RESULTS: The polyphenol acetates unlike the parent polyphenol caused time dependent inhibition of liver microsome catalyzed AFB1-binding to DNA. Accordingly the administration of polyphenols resulted in significant reduction in the incidence of AFB1-induced micronuclei and apoptosis in lung and bone marrow cells of rats. CONCLUSIONS: These results indicate that acetates of polyphenolics are superior to their deacetylated products and confirm our hypothesis that the microsome membrane bound acetoxy drug: protein transacetylase (identified for the first time in our laboratory) 1 act upon acetoxy polyphenols resulting in the possible acetylation of CYP-linked MFO, eventually leading to the prevention of genotoxicity due to AFB1.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prevention.