Tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland of fluorinated derivatives of benzo[a]pyrene and 3-methylcholanthrene

Ercole Cavalieri, Eleanor G Rogan, Sheila Higginbotham, Paolo Cremonesi, Shahrokh Salmasi

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Abstract

Comparative studies of tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland were conducted with benzo[a]pyrene (BP) and 3-methylcholanthrene (MC) derivatives. SENCAR mice were initiated with BP, 6-fluorobenzo[a]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.

Original languageEnglish (US)
Pages (from-to)16-22
Number of pages7
JournalJournal of Cancer Research and Clinical Oncology
Volume114
Issue number1
DOIs
StatePublished - Feb 1 1988

Fingerprint

Methylcholanthrene
Benzo(a)pyrene
Human Mammary Glands
Skin
Epoxy Compounds
Neoplasms
Sprague Dawley Rats
Inbred SENCAR Mouse
Injections
Acetates
trans-1,2-dihydro-1,2-naphthalenediol

Keywords

  • Fluorinated aromatic hydrocarbons
  • Mouse skin
  • Rat mammary gland
  • Tumorigenicity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland of fluorinated derivatives of benzo[a]pyrene and 3-methylcholanthrene. / Cavalieri, Ercole; Rogan, Eleanor G; Higginbotham, Sheila; Cremonesi, Paolo; Salmasi, Shahrokh.

In: Journal of Cancer Research and Clinical Oncology, Vol. 114, No. 1, 01.02.1988, p. 16-22.

Research output: Contribution to journalArticle

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abstract = "Comparative studies of tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland were conducted with benzo[a]pyrene (BP) and 3-methylcholanthrene (MC) derivatives. SENCAR mice were initiated with BP, 6-fluorobenzo[a]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.",
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