Tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland of fluorinated derivatives of benzo[a]pyrene and 3-methylcholanthrene |
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Authors: | Ercole Cavalieri Eleanor Rogan Sheila Higginbotham Paolo Cremonesi Shahrokh Salmasi |
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Institution: | (1) Eppley Institute for Research in Cancer, University of Nebraska Medical Center, 42nd Street and Dewey Avenue, 68105-1065 Omaha, NE, USA;(2) Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 42nd Street and Dewey Avenue, 68105-1065 Omaha, NE, USA |
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Abstract: | Summary Comparative studies of tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland were conducted with benzoa]pyrene (BP) and 3-methylcholanthrene (MC) derivatives. SENCAR mice were initiated with BP, 6-fluorobenzoa]pyrene (6-FBP), 6-methylBP, 7-FBP, 8-FBP, 9-FBP, 10-FBP, or 10-azaBP and promoted with tetradecanoyl phorbol acetate. The same compounds plus BP 7,8-dihydrodiol were tested by intramammillary injection in female Sprague-Dawley rats. Tumor-initiating activity in mice and/or carcinogenicity in rats were observed for BP, 6-methylBP, 6-, 7-, 8-, and 10-FBP, whereas 9-FBP was inactive in both experiments and 10-azaBP was only marginally active in the mammary gland. BP 7,8-dihydrodiol was carcinogenic in rat mammary gland, although it was less potent than BP. MC, 8-FMC, 10-FMC, and 3-methylcholanthrylene were also tested in Sprague-Dawley rats by intramammillary injection. All compounds were carcinogenic, with MC displaying the most potent activity. The less potent carcinogenic activity of BP 7,8-dihydrodiol in the mammary gland, compared with BP, and the moderate-to-weak tumor-initiating and/or carcinogenic activity of 7-, 8-, and 10-FBP suggest that the bay-region diol-epoxide pathway does not play a significant role in the activation of BP in these two target tissues. Similarly, the carcinogenic activity of 8-FMC and 10-FMC, in which the bay-region diol-epoxide pathway is blocked, suggests that this mechanism of activation is not important in the carcinogenicity of MC in rat mammary gland.Abbreviations used 10-azaBP
10-azabenzoa]pyrene
- BP
benzoa]pyrene
- BP 7,8-dihydrodiol
7,8-dihydroxy-7,8-dihydrobenzoa]pyrene
- 6-FBP
6-fluorobenzoa]pyrene
- 7-FBP
7-fluorobenzoa]pyrene
- 8-FBP
8-fluorobenzoa]pyrene
- 9-FBP
9-fluorobenzoa]pyrene
- 10-FBP
10-fluorobenzoa]pyrene
- 8-FMC
8-fluoro-3-methylcholanthrene
- 10-FMC
10-fluoro-3-methylcholanthrene
- 6-methylBP
6-methylbenzoa]pyrene
- MC
3-methylcholanthrene
- MCL
3-methylcholanthrylene
- PAH
polycyclic aromatic hydrocarbons
- TBA
tumor-bearing animals
Supported by Public Health Service grants CA32376 and CA36727 and a seed research grant from the University of Nebraska Medical Center |
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Keywords: | Mouse skin Rat mammary gland Tumorigenicity Fluorinated aromatic hydrocarbons |
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