Long chain fatty acids required for lipid synthesis are formed from acetyl CoA by the sequential actions of acetyle CoA carboxylase (ACC) and fatty acid synthase (FAS). Both these enzymes are present in mammary gland and mammary tumors. Upon lactogenesis the quantities of ACC and FAS increase about 40 to 50 fold over those found in virgin mammary tissue. The induction of ACC and FAS normally observed in differentiating mammary tissue does not occur when the transplantable mammary tumors (13762 and R3230AC) are carried by pregnant or lactating dams. The results of immunological studies show that ACC of mammary neoplasms is different from the normal tissue carboxylase. ACC and FAS provide useful markers for mammary gland differentiation. Therefore, experiments will be performed to identify the biological stimuli inducing these enzymes in mammary epithelial cells. Parallel studies will be conducted on the cell lines established from dissociated mammary neoplasms to determine whether the effects of these modulators (of lipogenesis) are modified or lost during tumorigenesis. Similarly, the chemical nature for the immunological difference observed between mammary gland and mammary tumor ACCs will be investigated. During involution the activities of ACC and FAS fall off extremely rapidly. The mechanism of degradation of these lipogenic enzymes will be studied. The regulation of biotination and the short-term control of acetyl CoA carboxylase in mammary epithelial cells, and in animals will also be studied.