PHOTOCHEMICALLY INDUCED BINDING OF AFLATOXINS TO DNA AND ITS EFFECTS ON TEMPLATE ACTIVITY

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (3) , 689-695
Abstract
The covalent binding of photoactivated aflatoxin B1 (AFB1) to DNA and its effect on template activity were investigated. AFB1 in its ground state complexes more preferentially with denatured DNA than with native DNA. The covalent linkage between 3H-AFB1 and DNA under near-UV light irradiation shows 1 AFB1 per 529 pi of calf thymus DNA. The photoaddition also induces a conformational change of the DNA, as detected by circular dichroism. Because the photobinding of AFB2 to DNA is negligible (1 AFB2 per 5485 Pi), it is suggested that the 8,9-C.dbd.C bond is the major binding site of AFB1. The AFB1-DNA adduct shows a substantial inhibition of its template activity for DNA synthesis (by 52%) and RNA transcription (by 74%) in vitro. Since AFB1 and AFB2 had little inhibitory effect on the activities of DNA and RNA polymerases, the alteration of DNA by photoactivated AFB1 and AFB2 is responsible for the dramatic reduction of template activity in DNA and RNA synthesis. Short-chain polynucleotides retained by type VS membrane filter (0.025 .mu.m pore size) indicate that premature chain termination occurred in transcribing the AFB1-DNA and AFB2-DNA adducts as the result of disrupted movement of the enzymes along the DNA chain.