摘要
Since the beginning of the 1980s, Dai Qianhuan predicted based upon his di-region theory that the carcino-genesis switched on by the so-called physical carcinogenic factors including radiation, asbestos and foreign matter implantation, is just initiated through the cross-linking between DNA complementary pair bases induced by them. In this note, it was evidenced with the DNA filter elution method that the oxygenase activated by asbestos induces the cross-linking between DNA inter-strands and DNA-protein with dosage correlation, in which over 80% of DNA inter-strand cross-link ratio account for the total cross-link ratio. Obviously, both of the cross-linkages are just induced by hydroxyl free radical, HO·, because the ferrous ion increased the cross-link ratios up to several times through Fenton reaction and vitamin C inhibited the cross-link ratios with factors of 8-9 by destroying the hydroxyl radical. Non-carcinogen but with lower free radical formation energy, pyrene, by culturing with asbestos
Since the beginning of the 1980s, Dai Qianhuan predicted based upon his di-region theory that the carcinogenesis switched on by the so-called physical carcinogenic factors including radiation, asbestos and foreign matter implantation, is just initiated through the cross-linking between DNA complementary pair bases induced by them. In this note, it was evidenced with the DNA filter elution method that the oxygenase activated by asbestos induces the cross-linking between DNA inter-strands and DNA-protein with dosage correlation, in which over 80% of DNA inter-strand cross-link ratio account for the total cross-link ratio. Obviously, both of the cross-linkages are just induced by hydroxyl free radical, HO ·, because the ferrous ion increased the cross-link ratios up to several times through Fenton reaction and vitamin C inhibited the cross-link ratios with factors of 8–9 by destroying the hydroxyl radical. Non-carcinogen but with lower free radical formation energy, pyrene, by culturing with asbestos gave 3–4 times cross-link ratios than the original ratios induced by asbestos only. Estradiol, an endogenous carcinogen, as a bio-electrophilic species but with higher free radical formation energy by culturing with asbestos, gave only 1.2 time cross-link ratios than expected ones. Ferrous ion which can increase HO · concentration through Fenton reaction, increased the ratios to 2–2.5 times in the former case but only 1.2 time in the latter case. Vitamin C, a free radical scavenger, gave a powerful inhibition to the cross-linking with a factor of 8–11 in the former case but a weak inhibition with a factor of 1.2 only in the latter case. So, it is evidenced further that the cross-linkages induced by asbestos are originated from hydroxyl radical. Reasonable structures of the cross-linking products induced by asbestos or hydroxyl radical have been depicted based upon AMI MO theory. These structures have been verified further by a reasonable explanation of the mutational spectrum induced by hydroxyl radical.
基金
This work was supported by the National Natural Science Foundation of China (Grant No. 20042001).
