Molecular dosimetry for carcinogens.
Krishnan SP; Warshawsky D; Talaska G; Livingston G
Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio 1995 Feb; :1-62
The relationship between DNA adducts and micronuclei (MN) was investigated in primary cultures of mouse keratinocytes treated with benzo(a)pyrene (50328) (BaP), 7H-dibenzo(c,g)carbazole (57976) (DBC), or 7,12-dimethylbenz(a)anthracene (57976) (DMBA). Primary cultures were established from female HSD:ICR(Br)-mice. Keratinocytes were incubated for 6 to 24 hours with BaP at 100, 150 or 750 nanograms (ng) per plate; DBC at 15, 150 or 1,500ng/plate; or DMBA at 48, 96, 192 or 384ng/plate. A strong statistical association was demonstrated between carcinogen/DNA adducts and MN for both DBC and DMBA, suggesting that the two end points may be causally related for both compounds. Results suggested that covalent modification of DNA may explain partly the induction of cytogenetically observable lesions for DBC as well as DMBA. The DMBA induced MN levels were at comparable levels to that of DBC or at some doses even higher, suggesting that DMBA has a tumorigenic potency higher than that of BaP by one order of magnitude. 7,8- Benzoflavone (7,8-BF) caused a partial inhibition of DBC induced MN, suggesting that some of the MN may have arisen by a mechanism independent of DNA adduct formation. The authors note that MN may arise as a result of loss of entire chromosomes due to damage to the spindle apparatus, which may explain the excess MN observed which could not be inhibited by 7,8-BF.
NIOSH-Grant; Cancer; Carcinogens; Laboratory-animals; DNA-adducts; Genotoxic-effects; In-vitro-studies; Polycyclic-aromatic-hydrocarbons
Environmental Health Univ of Cincinnati 3223 Eden Ave Cincinnati, OH 45267-0056
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Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio
University of Cincinnati, Cincinnati, Ohio