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 b...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%.展开更多
目的:研究胃萎方对信号转导及转录激活蛋白3(Signal Transducer and Activator of Transcription 3,STAT3)/核因子-κB(Nuclear Factor-κB,NF-κB)信号通路的调控作用,探讨胃萎方对胃癌前病变(Precancerous Lesion of Gastric Cancer,P...目的:研究胃萎方对信号转导及转录激活蛋白3(Signal Transducer and Activator of Transcription 3,STAT3)/核因子-κB(Nuclear Factor-κB,NF-κB)信号通路的调控作用,探讨胃萎方对胃癌前病变(Precancerous Lesion of Gastric Cancer,PLGC)的疗效及作用机制。方法:从70只雄性Wistar大鼠中随机选择20只作为空白组,其余50只为造模组。采用N-甲基-N’-硝基-N-亚硝基胍(MNNG)诱导GPL大鼠实验模型。14周后,对随机选择的造模组大鼠10只进行胃组织学分析,确认造模成功,造模组剩余40只大鼠随机分为模型组、胃萎方治疗组各20只。使用胃萎方干预后,观察大鼠体质量增长、胃黏膜组织结构变化,以及血清胃蛋白酶原(Pepsinogen,PG)Ⅰ,PGⅡ和胃泌素的浓度,并检测NF-κB p65和STAT3的基因及蛋白表达。结果:与空白组比较,模型组大鼠体质量增长缓慢,胃黏膜组织细胞异型增生明显,血清PGⅠ、胃泌素水平和PGⅠ/PGⅡ比值显著降低,胃黏膜NF-κB/STAT3信号通路被激活;与模型组比较,胃萎方治疗组大鼠整体情况改善,胃黏膜组织结构重塑、萎缩性胃黏膜和非典型腺上皮减少,PGⅠ/PGⅡ比值和胃泌素水平增加(P<0.01),NF-κB p65和STAT3的mRNA及蛋白的表达受到一定程度的抑制(P<0.05)。结论:胃萎方能够通过抑制NF-κB/STAT3信号通路逆转MNNG诱导的大鼠GPL,为胃萎方的临床应用提供了基础证据。展开更多
基金Project supported the National Natural Science Foundation of China.
文摘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%.
文摘目的:研究胃萎方对信号转导及转录激活蛋白3(Signal Transducer and Activator of Transcription 3,STAT3)/核因子-κB(Nuclear Factor-κB,NF-κB)信号通路的调控作用,探讨胃萎方对胃癌前病变(Precancerous Lesion of Gastric Cancer,PLGC)的疗效及作用机制。方法:从70只雄性Wistar大鼠中随机选择20只作为空白组,其余50只为造模组。采用N-甲基-N’-硝基-N-亚硝基胍(MNNG)诱导GPL大鼠实验模型。14周后,对随机选择的造模组大鼠10只进行胃组织学分析,确认造模成功,造模组剩余40只大鼠随机分为模型组、胃萎方治疗组各20只。使用胃萎方干预后,观察大鼠体质量增长、胃黏膜组织结构变化,以及血清胃蛋白酶原(Pepsinogen,PG)Ⅰ,PGⅡ和胃泌素的浓度,并检测NF-κB p65和STAT3的基因及蛋白表达。结果:与空白组比较,模型组大鼠体质量增长缓慢,胃黏膜组织细胞异型增生明显,血清PGⅠ、胃泌素水平和PGⅠ/PGⅡ比值显著降低,胃黏膜NF-κB/STAT3信号通路被激活;与模型组比较,胃萎方治疗组大鼠整体情况改善,胃黏膜组织结构重塑、萎缩性胃黏膜和非典型腺上皮减少,PGⅠ/PGⅡ比值和胃泌素水平增加(P<0.01),NF-κB p65和STAT3的mRNA及蛋白的表达受到一定程度的抑制(P<0.05)。结论:胃萎方能够通过抑制NF-κB/STAT3信号通路逆转MNNG诱导的大鼠GPL,为胃萎方的临床应用提供了基础证据。
