Ab initio Studies on the Carcinogenic Mechanism of the Derivatives of 3,5-Dimethyl-nitrosopiperazine

摘要

3,5-Dimethyl-nitrosopiperazine (DMNP) is a kind of cyclic nitrosamine which was recognized as environment carcinogens. The carcinogenic potency of DMNP was observed to be different when their N' atom was substituted with different groups. This distinction in the metabolic activation of α- and γ-position was reported to contribute to their distinct carcinogenicity. In this work, ab initio computations were carried out to study the carcinogenic mechanism of α- and γ-positions of DMNP and its derivatives. The results showed that the increase of the γ-position activity induced the decline of the carcinogenic potency. However, the influence of the α-position activity was ambivalent, the carcinogenic potency can be reduced either too high or too low activity on α-position. This study of the metabolic processes of the α- and γ-positions provided a theoretical evidence for the carcinogenic mechanism of cyclic nitrosamines.