Tumorigenicity of 6-halogenated derivatives of benzo[a]pyrene in mouse skin and rat mammary gland.
Tumorigenicity of 6-halogenated derivatives of benzo[a]pyrene in mouse skin and rat mammary gland.
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苯并[a]芘的 6-卤代衍生物在小鼠皮肤和大鼠乳腺中的致瘤性。
DOI：
10.1007/bf00390479
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发表时间：
1988
影响因子：
3.6
通讯作者：
Salmasi,S
中科院分区：
文献类型：
--
作者：
Cavalieri,E;Rogan,E;Cremonesi,P;Higginbotham,S;Salmasi,S
苯并[a]芘（BP）的6-卤化衍生物的致瘤性研究可以为6位在BP的致癌激活中的作用提供证据。用BP、6-氟苯并[a]芘（6-FBP）、6-氯苯并[a]芘（6-C1BP）、6-溴苯并[a]芘（6-BrBP）和6-碘苯并[a]芘（6-IBP）在雌性瑞士小鼠和a -品系小鼠皮肤上反复施用，在某些情况下采用起始促进法。虽然BP比6-FBP更有效，但只有这两种化合物在小鼠皮肤中表现出肿瘤启动和致癌活性。雌性Sprague-Dawley大鼠经乳腺内注射BP、6-FBP、6-C1BP和6-BrBP。BP和6-FBP诱导高水平的乳腺上皮肿瘤和纤维肉瘤。6-C1BP仅诱导高比例的纤维肉瘤，而6-BrBP诱导少数腺癌。这些结果表明，在BP中C-6的氯或溴取代降低或消除了致癌活性。相反，6-FBP，其中的氟取代基通过单电子氧化被化学和代谢去除，显示出中等的致癌活性，这与单电子氧化或单氧合的激活一致。
Studies of the tumorigenicity of 6-halogenated derivatives of benzo[a]pyrene (BP) can provide evidence about the role of the 6 position in the carcinogenic activation of BP. Female Swiss and A-strain mice were treated on the skin with BP, 6-fluorobenzo[a]pyrene (6-FBP), 6-chlorobenzo[a]pyrene (6-C1BP), 6-bromobenzo[a]pyrene (6-BrBP) and 6-iodobenzo[a]pyrene (6-IBP) by repeated application, and in some cases by initiation-promotion. While BP was more potent than 6-FBP, only these two compounds exhibites tumor-initiating and carcinogenic activity in mouse skin. Female Sprague-Dawley rats were treated with BP, 6-FBP, 6-C1BP, and 6-BrBP by intramammillary injection. BP and 6-FBP induced high levels of mammary epithelial tumors and fibrosarcomas. 6-C1BP elicited only a high percentage of fibrosarcomas, whereas 6-BrBP induced a few adenocarcinomas. These results indicate that chloro or bromo substitution at C-6 in BP reduces or eliminates carcinogenic activity. Conversely, 6-FBP, from which the fluoro substituent has been chemically and metabolically removed by one-electron oxidation, displays a moderate carcinogenic acitivity which is consistent with activation by either one-electron oxidation or monooxygenation.