Summary
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.
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Abbreviations
- BP:
-
benzo[a]pyrene
- 6-BrBP:
-
6-bromobenzo[a]pyrene
- 6-C1BP:
-
6-chlorobenzo[a]pyrene
- 6-FBP:
-
6-fluorobenzo[a]pyrene
- 6-IBP:
-
6-iodobenzo[a]pyrene
- 6-OAcBP:
-
6-acetoxybenzo[a]pyrene
- PAH:
-
polycyclic aromatic hydrocarbons
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Supported by Public Health Service contract NO1 CPO5620 and grants 1 RO1 CA32376 and Laboratory Cancer Research Center Core Grant CA36727 from the National Cancer Institute
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Cavalieri, E., Rogan, E., Cremonesi, P. et al. Tumorigenicity of 6-halogenated derivatives of benzo[a]pyrene in mouse skin and rat mammary gland. J Cancer Res Clin Oncol 114, 10–15 (1988). https://doi.org/10.1007/BF00390479
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DOI: https://doi.org/10.1007/BF00390479