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An intermediate is invoked to explain the formation of interstrand cross-links when the DNA is treated by nitrous acid. The cross-links appear with a time lag, and they continue to form after elimination of the nitrous acid. The concentration of the intermediate quickly reaches a steady state during the nitrous acid treatment. After a time lag of a few minutes, the appearance of cross-links follows zero order kinetics; moreover, the maximum increase of cross-links during post-treatment incubation is independent of the duration of nitrous acid treatment as soon as it exceeds a few minutes. As a pH decrease favors the DNA cross-linking either during the nitrous acid treatment or during the post-treatment incubation, it is proposed that a free aldehyde group plays a role in the reaction mechanism, and a reaction scheme is presented which involves deamination of guanine to xanthine, depurination of xanthine, and subsequent reaction of the liberated aldehyde function with an amino group of the opposite DNA chain. Finally, the lethal action of HNO2 on bacteriophages is also discussed.
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Burnotte et al. (1971) studied this question.
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