Carcinogenesis of asbestos switched on by inducing cross-linkage between DNA complementary pair bases |
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Authors: | Qianhuan Dai Sha Chen Yingxia Li |
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Institution: | (1) Center of Environmental Science, Peking University, 100871 Beijing, China;(2) Center for Chemistry and Bioengineering of Cancer, Beijing Polytechnic University, 100022 Beijing, China |
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Abstract: | 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. |
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Keywords: | asbestos mechanism of carcinogenesis di-region theory hydroxyl free radical DNA interstrand cross-link Fenton reaction AMI molecular orbital calculation |
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