Mutagenicity and tumor-initiating activity of fluorinated derivatives of 7,12-dimethylbenz(a)anthracene

Eliezer Huberman, Thomas J. Slaga

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61 Scopus citations


7,12-Dimethylbenz(a)anthracene (DMBA) and its 1-, 2-, 5-, and 11-fluoro derivatives were tested to determine their mutagenicity for ouabain resistance in Chinese hamster V79 cells and their tumor-initiating activity in mouse skin. Inasmuch as V79 cells do not metabolize polycyclic aromatic hydrocarbons, mutagenesis was tested both in the presence and in the absence of golden hamster embryo cells capable of metabolizing polycyclic aromatic hydrocarbons. Neither DMBA nor any of the fluorinated derivatives showed mutagenicity for V79 cells in the absence of the golden hamster cells. In the presence of these cells, DMBA and 11-fluoro-DMBA exhibited a comparable mutagenic response that was dose dependent. At a dose as low as 0.01 μM, a 7-to 10-fold increase in the frequency of ouabain-resistant mutants was observed. The other derivatives were either inactive or required more than a 1000-fold higher dose to induce a comparable mutagenic response. Similarly, both DMBA and 11-fluoro-DMBA at 100 nmol initiated tumors in 100% of the tested mice, whereas the other fluorinated derivatives at this dose initiated skin tumors in 15% or less of the treated mice. The average number of papillomas per mouse induced by 1-, 2-, and 5-fluoro-DMBA was more than 100-fold lower than the number induced by DMBA or 11-fluoro-DMBA. These results suggest that carbon positions 1 and 2 of DMBA, which are located at the “bay region,” and position 5, which is located at the “K-region,” are involved in the metabolic activation of DMBA into mutagenic and carcinogenic metabolites.

Original languageEnglish (US)
Pages (from-to)411-414
Number of pages4
JournalCancer Research
StatePublished - Feb 1 1979
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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