Study On DNA Crosslinkage Induced By Asbestos

Di-region theory, a reasonable explanation of the mechanism of chemical carcinogenesis, has been put forward by Professor Dai Qianhuan in 1979. Di-region theory discovered that the crosslinking between DNA complementary pair bases induced by the metabolized carcinogen is the key step of the chemical carcinogenesis. It is evidenced by epidemiological investigations and animal tests that the asbestos posses powerful carcinogenic potential, especially the ability of inducing lung cancer. Dai Qianhuan predicted based upon his di-region theory that the carcinogenesis switched on by the so-called physical carcinogenic factors including asbestos and foreign matter implantation, is just initiated through the crosslinking between DNA complementary pair bases induced by them. Asbestos may cause two types of DNA interstrand crosslinking: One is initiated by hydroxyl free radical, and the other one is initiated theoretically by asbestos itself according to electrophilic theory. The goal of this paper is to find out whether asbestos may cause DNA interstrand crosslinking and initiate it by active oxide - free radical.In this paper, it was evidenced with DNA filter elution method that the oxygenase activated by asbestos induces the crosslinking between DNA interstrands and DNA-protein with dosage correlation, in which over 80% of DNA interstrand crosslink ratio in total crosslink ratio is achieved. Obviously, all of the crosslinkages are just induced by hydroxyl free radical, HO, because estradiol, an endogenous carcinogen, seems to increase the crosslinking ratio with the rise of its dose, non-carcinogen but with lower free radical formation energy, pyrene, can't induce DNA crosslinking by culturing with cell solely, the ferrous ion increased the crosslink ratios up to several times through Fenton reaction and the vitamin C inhibited the crosslink ratios by destroying the hydroxyl free radical. Pyrene and estradiol can give increased crosslink ratios differently when they are cultured with asbestos separately. Ferrous ion can also increase crosslink ratios induced by asbestos-pyrene or asbestos-estradiol and vitamin C can inhibit crosslinking induced by asbestos, asbestos-pyrene or asbestos-estradiol to some extent. So, it is evidenced further that the crosslinkages induced by asbestos are originated from hydroxyl free radical.