Anthracene becomes covalently bound to high-molecular-weight DNA in mammalian tissue culture as a result of irradiation at 365 nm after the incubation of cells with the hydrocarbon. At high radiation doses, the extent of binding exceeds one hydrocarbon molecule per 10(3) bases, and is lethal. At low radiation doses, much decreased binding is observed, but a majority of cells remain viable and can be recultured.
The distribution of tritium in generally-labelled benzo[a]pyrene is determined for positions 1, 4-5, and 6 by transformation into its 1-acetyl-, [4,5-b]quinoxalino-, and 6-nitro-derivatives; the extent of loss of tritium from the same hydrocarbon on binding to DNA either photochemically in vitro or metabolically in vivo shows that these processes are not associated with the K-region of the hydrocarbon, but are most likely to result from covalent substitution a t position 6 or 1.
Anthracene can be bound covalently to calf thymus deoxyribonucleic acid (DNA) by means of long-wavelength U.V. irradiation to a greater extent than any other of seven polycyclic aromatic hydrocarbons investigated. 3H is incorporated into the photochemical product resulting from the irradiation of doubly labelled hydrocarbons and DNA to a lesser extent than is 14C. In the case of anthracene, the ratio of incorporation of the two isotopes is ca.3:4 and is independent of the extent of irradiation or of hydrocarbon binding. The relevance of these results to the mechanism of binding of hydrocarbons to DNA and to the photodynamic carcinogenicity of anthracene is discussed briefly.Chemistry, The University, Sheffield S3 7HF COVALENT binding or polycyclic aromatic hydrocarbons to the deoxyribonucleic acid (DNA) of mammalian skin i uc vivo was first observed by Heidelberger and Davenport in the case of dibenz[a,h]anthracene and was later established as providing a satisfactory correlation with carcinogenicity for a variety of such hydrocarbons.2The mechanism of such covalent attachment is not known, although much recent activity has centred on the possible role of aromatic hydrocarbon epoxides as potential ultimate carcinogens since such compounds are known intermediates in the conversion of the aromatic hydrocarbons into the corresponding dihydrodiols by liver Several model systems have been developed to effect covalent binding of these hydrocarbons to native and to denatured DNA in vitro. These methods include radiation by u.v.,* X-rayQ and y lo sources, iodine,11J2 hydrogen peroxide,11J3 and ascorbic acidll oxidising systems, and also some combination of these.14In general, the results from these models have been interpreted to show that the more carcinogenic hydrocarbons could be bonded to DNA to a greater extent than their non-carcinogenic i~orners.*J~~~* In addition, the majority of these results have relied on a radioisotope assay involving the incorporation of tritiated aromatic hydrocarbon into the DNA. On the other hand, the elucidation of structures for the photoproducts formed between benzo[a]pyrene and l-methylcytosine l5 and thymine l6 has shown that they arise from an oxidative coupling between hydrocarbon and nucleic acid base which necessarily involves the loss of hydrogen from the hydrocarbon. Accordingly, there must be some uncertainty about the reliability and accuracy of the tritium-incorporation assay.This paper reports a re-evaluation of the extent of
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