Relationship of DNA repair processes to mutagenesis and carcinogenesis in mammalian cells. Progress report, November 1, 1978-October 31, 1979. [EMS; cultured mouse embryo cells (C3H/10T 1/2)

Abstract

The objective of this research is to determine the role of DNA repair in mutagenesis and carcinogenesis in mammlian cells. Repair capabilities will be varied by: (1) using wild-type and repair-deficient cell lines; (2) imposing various recovery periods following mutagenic treatment; (3) exposing cells to inhibitors of DNA repair following mutagenic treatment; and (4) varying the mutagenic treatment to cause DNA lesions repairable by different pathways. Reconstruction experiments were conducted to (1) investigate conditions for measuring transformation frequency using colony formation, and (2) determine the influence of ouabain-sensitive cells on the expression of ouabain-resistance. Ouabain-resistant cells were isolated from EMS-treated cultures and were shown to be resistant to the drug with regard to survival and the activity of the Na/sup +/-K/sup +/-ATPase. The effect of holding EMS-treated cells under various conditions which do not allow DNA synthesis was determined with respect to survival and the incidence of transformation and mutation. When confluent cells were held for 4 hrs following EMS treatment, both survival and the frequency of transformation increased. When the cells were incubated in 0.1% serum for 6 hrs following EMS treatment, no change in either the transformation or mutation frequency was observed as compared to cells incubated inmore » 10% serum. Further experiments are in progress to determine the effect of recovery periods on transformation and mutation frequencies.« less