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Molecular Dosimetry for Carcinogens.


PB95270054

Publication Date 1995
Personal Author Krishnan, S. P.; Warshwsky, D.; Talaska, G.; Livingston, G.
Page Count 64
Abstract 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:ISR(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 1,500 ng/plate; or DMBA at 48, 96, 192 or 38 ng/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 to 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 DBC or at some 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 risen by a mechanism independent adducted formation. The authors note that MN may arise as a result of loss 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.
Keywords
  • Carcinogens
  • Cancers
  • Mice
  • Laboratory animals
  • Genatoric effects
  • In vitro analysis
  • DNA adducts
  • Micronuclei
  • Polycyclic aromatic hydrocarbons
Source Agency
  • National Institute for Occupational Safety and Health
NTIS Subject Category
  • 57Y - Toxicology
  • 57F - Cytology, Genetics, & Molecular Biology
Corporate Authors Cincinnati Univ., OH. Dept. of Environmental Health.; National Inst. for Occupational Safety and Health, Cincinnati, OH.
Supplemental Notes Sponsored by National Inst. for Occupational Safety and Health, Cincinnati, OH.
Document Type Technical Report
NTIS Issue Number 199523
Molecular Dosimetry for Carcinogens.
Molecular Dosimetry for Carcinogens.
PB95270054

  • Carcinogens
  • Cancers
  • Mice
  • Laboratory animals
  • Genatoric effects
  • In vitro analysis
  • DNA adducts
  • Micronuclei
  • Polycyclic aromatic hydrocarbons
  • National Institute for Occupational Safety and Health
  • 57Y - Toxicology
  • 57F - Cytology, Genetics, & Molecular Biology
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