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

Journal Article · Thu Feb 01 04:00:00 EST 1979 · Cancer Res.; (United States)

OSTI ID:5059493

Huberman, E; Slaga, T J

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 ..mu..m, 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.

• Research Organization: Oak Ridge National Lab., TN
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 5059493
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 39; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550300 -- Cytology
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BODY
CARBOHYDRATES
CARCINOGENESIS
CARDIOTONICS
CELL CULTURES
CONDENSED AROMATICS
DIMETHYLBENZANTHRACENE
DOSE-RESPONSE RELATIONSHIPS
DRUGS
EMBRYOS
ENZYME ACTIVITY
GLYCOSIDES
HAMSTERS
MAMMALS
METABOLITES
MICE
MUTAGENESIS
ORGANIC COMPOUNDS
ORGANS
OUABAIN
PATHOGENESIS
RODENTS
SENSITIVITY
SKIN
STEROIDS
STROPHANTIN
TOXICITY
VERTEBRATES