Relationship between DNA adduct formation and unscheduled DNA synthesis (UDS) in cultured mouse epidermal keratinocytes
- Univ. of Texas M.D. Anderson Cancer Center, Smithville (United States)
- Chemical Industry Inst. of Toxicology, Research Triangle Park, NC (United States)
Primary cultures of mouse epidermal keratinocytes from SENCAR mice were treated with 7,12-dimethylbenz(a)anthracene (DMBA), benzo(a)pyrene (B(a)P), ({plus minus}) 7{beta}-8{alpha}-dihydroxy-9{alpha},10{alpha}-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (({plus minus}) anti-BPDE), and ({plus minus}) 7{beta},8{alpha}-dihydroxy-9{beta},10{beta}-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (({plus minus})syn-BPDE) to examine the relationship between DNA adduct formation and the induction of unscheduled DNA synthesis (UDS). DNA adducts were measured as pmol hydrocarbon bound per mg of DNA, and UDS was quantitated autoradiographically as net grains per nucleus. A good correlation was observed between the levels of UDS detected and the amount of DNA adducts present int he cell population when comparing similar compounds within the linear dose-response range of 0.005 {mu}g/ml-0.25 {mu}g/ml. These results suggest that the present UDS assay with MEKs is a useful assay for the rapid screening of potential genotoxic agents. However, the limits of sensitivity are such that the current assay may be unable to detect a low level of DNA damage induced by some weakly genotoxic (carcinogenic) agents. In addition, while the limits of sensitivity determined in these experiments apply to the polycyclic aromatic hydrocarbon class, other classes of genotoxic compounds such as alkylating agents or crosslinking agents may exhibit different thresholds of detection.
- OSTI ID:
- 6097515
- Journal Information:
- Environmental and Molecular Mutagenesis; (United States), Vol. 18:3; ISSN 0893-6692
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DNA ADDUCTS
BIOASSAY
DNA REPLICATION
EPIDERMIS
AUTORADIOGRAPHY
POLYCYCLIC AROMATIC HYDROCARBONS
BIOLOGICAL EFFECTS
BENZOPYRENE
DIMETHYLBENZANTHRACENE
DNA REPAIR
KERATIN
MICE
TRITIUM COMPOUNDS
ADDUCTS
ANIMAL TISSUES
ANIMALS
AROMATICS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CONDENSED AROMATICS
EPITHELIUM
HYDROCARBONS
HYDROGEN COMPOUNDS
MAMMALS
NUCLEIC ACID REPLICATION
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RECOVERY
REPAIR
RODENTS
SCLEROPROTEINS
SKIN
TISSUES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology