BIOCHEMICAL AND MORPHOLOGIC PROPERTIES OF A NEW LACTATING MAMMARY TUMOR LINE IN THE RAT.

Abstract

A new transplantable mammary adenocarcinoma of the Fischer rat has been studied. It arose spontaneously from the R3230AB, a faster growing, lactating tumor that was previously characterized. The new subline, the R3230AC, is autonomous-responsive and is composed primarily of epithelial cell elements. A copious lactational state is achieved in response to estrogen treatment and lactation is accompanied by a decrease in tumor growth rate. Androgen treatment will also decrease tumor growth rate. The tumor is less responsive to hormone treatment when this treatment is begun 15–30 days after implantation of the neoplasm. The characteristic extensive secretory epithelial cell activity, as induced by estrogen, is depressed by androgen treatment. Biochemical studies showed that 2- to 3-fold increases in glucose-6-phosphate dehydrogenase and triphosphopyridine nucleotide (TPN)-malic enzyme activities accompanied the estrogen-induced lactational response. The increase in these enzymes was observed within 3 days following estrogen treatment. Androgen treatment significantly depressed the activities of these 2 dehydrogenase enzymes below control levels. Isocitric dehydrogenase activity was not significantly altered. No significant anaerobic glucose utilization in vitro was obtained by the R3230AC tumor, nor did treatment with estrogen alter the utilization of glucose substrate. On the other hand, in vitro malic acid substrate utilization was demonstrated and estrogen treatment induced increased malic acid utilization. The R3230AC mammary carcinoma was compared to mammary glands of the same animals. Estrogen treatment markedly increased glucose-6-phosphate dehydrogenase, TPN-malic enzyme and isocitric dehydrogenase activities. Mammary glands did not utilize glucose in vitro under anaerobic conditions, but they did utilize malic acid substrate under these conditions. These data suggest that the R3230AC tumor is a transplantable breast neoplasm with certain biochemical and morphologic characteristics similar to normal breast tissue.