Abstract：
:To analyze the distribution of radioactive carcinogens and [3H]thymidine between nuclear DNA (nDNA) and mitochondrial DNA (mtDNA), we have developed a simple and rapid method for the separation of nDNA and mtDNA using gel electrophoresis of cell lysates. Using this method, we found that, when C3H10T 1/2 cells are exposed to either 0.5 microM [3H]-(+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene ([3H]BPDE) or 1 microM [3H]benzo(a)pyrene, the mtDNA contains a major fraction of the total adducts formed with cellular DNAs. Deoxynucleoside adducts formed between benzo(a)pyrene and mtDNA in intact C3H10T 1/2 cells or between BPDE and isolated rat liver mtDNA were analyzed by high-performance liquid chromatography, and were found to be much more heterogeneous than those present in nDNA of C3H10T 1/2 cells. The extensive modification of mtDNA in BPDE in C3H10T 1/2 cells is associated with preferential inhibition of the incorporation of [3H]thymidine into mtDNA, when compared to incorporation of [3H]thymidine into nDNA. To analyze the factors responsible for the extensive modification of mtDNA by BPDE, we investigated the role of a lipid phase utilizing liposome:DNA complexes as a model system. We found that the liposomes protect BPDE from spontaneous hydrolysis and enhance the extent of DNA modification at low DNA concentrations. These findings extent previous evidence suggesting that the mitochondria may be important cellular targets in the process of chemical carcinogenesis.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Backer JM,Weinstein IBsubject
Has Abstractpub_date
1982-07-01 00:00:00pages
2764-9issue
7eissn
0008-5472issn
1538-7445journal_volume
42pub_type
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