TY - JOUR
T1 - Tumorigenicity of 6-halogenated derivatives of benzo[a]pyrene in mouse skin and rat mammary gland
AU - Cavalieri, E.
AU - Rogan, E.
AU - Cremonesi, P.
AU - Higginbotham, S.
AU - Salmasi, S.
PY - 1988/2
Y1 - 1988/2
N2 - 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.
AB - 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.
KW - 6-Halogenated benzo[a]pyrenes
KW - Mouse skin
KW - Rat mammary gland
KW - Tumorigenicity
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U2 - 10.1007/BF00390479
DO - 10.1007/BF00390479
M3 - Article
C2 - 3350835
AN - SCOPUS:0023853009
VL - 114
SP - 10
EP - 15
JO - Zeitschrift fur Krebsforschung und Klinische Onkologie
JF - Zeitschrift fur Krebsforschung und Klinische Onkologie
SN - 0171-5216
IS - 1
ER -