INTERACTION OF BENZO(A)PYRENE AND ITS DIHYDRODIOL-EPOXIDE DERIVATIVE WITH NUCLEAR AND MITOCHONDRIAL-DNA IN C3H10T1/2 CELL-CULTURES

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (7) , 2764-2769
Abstract
To analyze the distribution of radioactive carcinogens and [3H]thymidine between nuclear DNA (nDNA) and mitochondrial DNA (mtDNA), a simple and rapid method was developed for the separation of nDNA and mtDNA using gel electrophoresis of cell lysates. Using this method, when C3H10T1/2 cells are exposed to either 0.5 .mu.M [3H]-(.+-.)-7.beta., 8.alpha.-dihydroxy-9.alpha.,10.alpha.-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene ([3H]BPDE) or 1 .mu.M [3H]benzo(a)pyrene, the mtDNA contains a major fraction of the total adducts formed with cellular DNA. Deoxynucleoside adducts formed between benzo(a)pyrene and mtDNA in intact C3H10T1/2 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 C3H10T1/2 cells. The extensive modification of mtDNA with BPDE in C3H10T1/2 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, the role of a lipid phase was investigated utilizing liposome: DNA complexes as a model system. The liposomes protect BPDE from spontaneous hydrolysis and enhance the extent of DNA modification at low DNA concentrations. The mitochondria may be important cellular targets in the process of chemical carcinogenesis.

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