Project Title: 14, Scope: Molecular and Cellular Radiobiology The Chemistry and Function of DNA Polymerases (Cont'd.) RX-03-02-(a) maturation of frog oocytes. As stated above an effort is underway to isolate and characterize at least omeenzyme with RNA-directed DNA synthesis from chick embryos. When the RNA directed-DNA polymerase has been isolated and purified it may be possible to develop or discover specific enzymatic inhibitors which would be of great help in determining its function in vivo. An attempt will be made to discover possible naturally-derived hybrid polymers which would serve as template-primers for the polymerase. (At present the only known hybrids with which the enzyme will function are synthetic polynucleotides.) Among possible naturally derived hybrids which might function in this capacity are hybrids of chick embryo messenger or ribosomal RNA with chick embryo DNA, the product of the action of RNA polymerase on chick embryo DNA, and chromatin isolated from chick embryo nuclei which is reported to contain RNA. A second research effort is directed at the general question of whether the induction of cumors by radiation (or by chemical carcinogens) is effected by the unmasking of a virus which may be present within the cell. Particles which appear to be identical to the type B mouse mammary tumor virus have been observed in human milk and in human mammary carcinomas. These particles. have been detected with high frequency in the milk of women with a family : history of breast cancer, but with low frequency in the milk of women without’ such family history. Type C particles have been isolated from a transplantable rat mammary adenocarcinoma derived originally from a spontaneous tumor which appeared in an aged Sprague-Dawley rat. Although these particles are capable of bringing about a transformation of rat mammary gland cells in tissue culture, there is no convincing evidence that they are able to produce mammary tumors when inoculated into young rats, Further, it has not proved possible to induce tumors by permitting young rats to nurse from mothers bearing radiation-induced mammary Cumors, Radiation- or dibenzanthracene-induced tumor tissue and che milk of lactating rats bearing such tumors are studied for “reverse transcriptase" associated with a 70S RNA and/or with a particle of density about 1.16 g/cc, characteristic of RNA viruses. particles will be undertaken, An electron microscopic search for such If evidence for the occurrence of virus-like Bles is obtained, efforts will be directed to the question of whether jresence, or the appearance of "reverse transcriptase" is useful in ing which rats in an irradiated group will develop tumors. If successful the rat model may become very useful for determining factors that may be revelant to human breast cancer, Some studies have already been carried out on a hybrid template-directed DNA polymerase from rat mammary tumors (see below). This polymerase is (See Continuation Sheet) 1119218 RX-218