DNA Polymerase Activity and DNA Synthesis in Preneoplastic Nodule Out-growths of BALB/c and C3H Mouse Mammary Gland2

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Abstract
DNA polymerase activity and DNA synthesis in 4 outgrowth lines of preneoplastic nodules (HAN) of BALB/c and C3H mouse mammary gland were determined. The rate of 3H-thymidine triphosphate (3H-dTTP) incorporation into trichloroacetic acid-insoluble material in vitro was used as a measure of DNA polymerase (DNA nucleotidyl transferase) activity in the postmicrosomal supernatant fraction of the HAN tissues. Incorporation of 3H-thymidine into DNA after a single intraperitoneal injection of the DNA precursor was used as a measure of DNA synthesis in the HAN cells in vivo. Both DNA polymerase and DNA synthesis in MTV-free and MTV-positive D1 nodule outgrowths of BALB/c mice were low. A relatively higher DNA polymerase activity and DNA synthesis were observed in the high tumor-producing, MTV-free D8 nodule of BALB/c mice. The highest level of DNA polymerase activity and DNA synthesis was in the high tumor-producing, MTV-positive CH33 nodule outgrowth line of C3H mice. Unlike the normal mouse mammary cells, both DNA polymerase activity and DNA synthesis in the preneoplastic lesions were independent of the ovarian hormones. The HAN outgrowth lines of both BALB/c and C3H mice, regardless of their tumorigenic potential, exhibit an altered responsiveness to normal regulation on DNA polymerase and DNA synthetic activities. The significance of this characteristic loss of normal control to suppress DNA polymerase and DNA synthesis in the preneoplastic lesions with regard to neoplastic transformation was discussed.

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