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Title: Detection of cellular DNA adducts in human fibroblasts treated with A-ring saturated and A-NCR-DMBA

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6997667

Previous reports from these laboratories revealed that 1,2,3,4-tetrahydro 7,12-dimethylbenz(a)anthracene (TH-DMBA) and 6,11-dimethylcyclopentano(a)anthracene (CP-DMA) transform human fibroblasts to an abnormal phenotype. The parent PAH 7,12-DMBA does not transform these cells. Since 7,12-DMBA but not TH-DMBA or CP-DMA is anticipated to form active bay region diol epoxides, they investigated whether the A-ring analogues form adducts with cellular DNA, when the cells are treated in S phase of the cell cycle. Treatment for 10 hr was carried out when the cells exhibited S phase entry i.e. 10 hr after Gl release from a nutritionally deficient block. Adducts were isolated using a modification of the /sup 32/P-post-labeling technique. Preliminary results indicate that TH-DMBA formed two different nucleotide adducts where as there were three different adducts identified with CP-DMA. These results suggest the level of modification to be circa 1-2 adducts/10/sup 7/ total nucleotides for TH-DMBA and 2-4 adducts/10/sup 7/ total nucleotides for CP-DMA. The present evidence accumulated to date strongly suggests that alternate mechanisms exist to oxygenate the FAH to reactive intermediates that subsequently form specific DNA adducts.

Research Organization:
Ohio State Univ., Columbus
OSTI ID:
6997667
Report Number(s):
CONF-8606151-; TRN: 87-004068
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
Country of Publication:
United States
Language:
English