QUANTITATIVE PATTERN RECOGNITION FOR STRUCTURE-CARCINOGENIC ACTIVITY RELATIONSHIP OF N-NITROSO COMPOUNDS BASED UPON DI-REGION THEORY  

作　　者：戴乾圜 钟儒刚 

机构地区：[1]Center for Chemistry & Bioengineering of Cancer, Beijing Polytechnic University

出　　处：《Science China Chemistry》1989年第7期776-790,共15页中国科学（化学英文版）

基　　金：Project supported the National Natural Science Foundation of China.

摘　　要：In this paper, it is evidenced by the quantitative structu re-carcinogenic activity relation-ship (QSCAR) and the pattern recognition treatment of N-nitroso compounds (NNC) that thekey step of carcinogenesis induced by NNC is the cross-linking on the complementary basepair of DNA, through the bifunctional alkylation between α-carbon and another carbonwithin the same chain. The alkylation by the α-carbon atom is through the diazonium salt,but that by the atom other than the α-position is through the active ester formed from thehydroxylated metabolite of the chain. Therefore, the alkylation by the β-position of NNC,or by its γ-position under suitable conditions, of which the distances from the α-positionboth approach 2. 80-3. 00 A, would be the most favourable positions along with the α-posi-tion for the cross-linking to occur between the complementary base pairs of DNA, whichwill yield the carcinogenic activity of NNC. The above conception of bifunctional alkyla-tion can reduce the QSCAR of NNC to a reasonable structure-chemical reactivity relationshipunder the complex biological conditions, and is the successful extension of the Di-regiontheory to the carcinogenesis mechanism of the important NNC series. In the light of theabove viewpoint, for 153 NNCs including the nitrosamines and nitrosamides which havebeen tested reliably with animals, the correct discrimination ratio by quantitative patternrecognition according to carcinogenic activity indexes divided into 5 degrees comes up to ashigh as 97%.In this paper, it is evidenced by the quantitative structu re-carcinogenic activity relation-ship (QSCAR) and the pattern recognition treatment of N-nitroso compounds (NNC) that thekey step of carcinogenesis induced by NNC is the cross-linking on the complementary basepair of DNA, through the bifunctional alkylation between α-carbon and another carbonwithin the same chain. The alkylation by the α-carbon atom is through the diazonium salt,but that by the atom other than the α-position is through the active ester formed from thehydroxylated metabolite of the chain. Therefore, the alkylation by the β-position of NNC,or by its γ-position under suitable conditions, of which the distances from the α-positionboth approach 2. 80-3. 00 A, would be the most favourable positions along with the α-posi-tion for the cross-linking to occur between the complementary base pairs of DNA, whichwill yield the carcinogenic activity of NNC. The above conception of bifunctional alkyla-tion can reduce the QSCAR of NNC

关 键 词：N-nitroso COMPOUNDS Di-region theory pattern recognition chemical CARCINOGENESIS structure-carcinogenic activity relationship 

分 类 号：O6[理学—化学]