Abrogation of killing and neoplastic transformation of C3H10T1/2 cells due to 7,12-dimethylbenz[a]anthracene. 1992

R L Wells, and C C Chen, and M M Elkind
Department of Radiological Health Sciences, Colorado State University, Fort Collins 80523.

The combined action of 7,12-dimethylbenz[a]anthracene (DMBA) and alpha-naphthoflavone (alpha NF) on the survival and neoplastic transformation of C3H10T1/2 mouse embryo fibroblasts has been examined and correlated with DNA adduct formation and removal. When a 24 h DMBA treatment of asynchronously growing cells was followed for the next 24 h by a treatment with alpha NF + DMBA, both killing and transformation per viable cell were abrogated to a large extent. In some instances, transformation was completely abrogated--i.e. reduced to control frequencies--even at nontoxic concentrations of DMBA, indicating that changes in survival were not the reason for the reduction in transformation. Even at toxic concentrations of DMBA, post-treatment with alpha-NF + DMBA resulted in 10-fold reductions in transformation frequency. 3-Methylcholanthrene (3MC) also reversed DMBA cytotoxicity but with a dependence on 3MC concentration that was qualitatively different from that for alpha NF. The abrogation of cell killing occurred at lower molar ratios of alpha NF:DMBA than the abrogation of transformation; less than or equimolar concentrations resulted in maximal abrogation of killing, but about equal concentrations were required to abrogate transformation. Although the preceding findings suggest that different mechanisms may be involved in these endpoints, taken together they suggest that second treatments make apparent the repair of lesions due to a first treatment with DMBA alone. To test this hypothesis, the formation and removal of DMBA-DNA adducts were measured. Adducts were not removed when the second treatment was growth medium alone, but enhanced removal was observed when second treatments consisted of DMBA alone or DMBA plus one of several other polycyclic aromatic hydrocarbons (PAHs). Relative to killing and neoplastic transformation, these results suggest DMBA induces a repair process that limits its own effectiveness--a process that can be sustained by other PAHs.

UI MeSH Term Description Entries
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002471 Cell Transformation, Neoplastic Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill. Neoplastic Transformation, Cell,Neoplastic Cell Transformation,Transformation, Neoplastic Cell,Tumorigenic Transformation,Cell Neoplastic Transformation,Cell Neoplastic Transformations,Cell Transformations, Neoplastic,Neoplastic Cell Transformations,Neoplastic Transformations, Cell,Transformation, Cell Neoplastic,Transformation, Tumorigenic,Transformations, Cell Neoplastic,Transformations, Neoplastic Cell,Transformations, Tumorigenic,Tumorigenic Transformations
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001571 Benzoflavones Organic compounds containing a BENZENE ring attached to a flavone group. Some of these are potent arylhydrocarbon hydroxylase inhibitors. They may also inhibit the binding of NUCLEIC ACIDS to BENZOPYRENES and related compounds. The designation includes all isomers; the 7,8-isomer is most frequently encountered. Benzoflavone Compounds,Compounds, Benzoflavone
D015127 9,10-Dimethyl-1,2-benzanthracene Polycyclic aromatic hydrocarbon found in tobacco smoke that is a potent carcinogen. 7,12-Dimethylbenzanthracene,7,12-Dimethylbenz(a)anthracene,7,12 Dimethylbenzanthracene
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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