Uptake and clearance of 9, 10-dimethyl-1, 2-benzanthracene-9-14C by mammary parenchymal cells of the rat.

Abstract

Groups of 50-day-old virgin female Sprague-Dawley rats received a single oral administration of 20 mg 9,10-dimethyl-1,2-benzanthracene and 50 µCi 9,10-dimethyl-1,2-benzanthracene-9-14C in 1 ml sesame oil and were sacrificed at various hours after carcinogen feeding. The abdominalinguinal mammary glands from the right side of the rat were used to determine the radioactivity contained within the mammary teat, fat pad, and vascular areas. The mammary glands from the left side were enzymatically separated into mammary parenchymal cell and fat cell fractions with collagenase. Intracellular lipid of the parenchymal cells was extracted and subjected to quantitative determination. The dry, lipid-extracted residue contained the radioactivity insoluble in lipid solvents. Maximum specific activity of the mammary parenchymal cell fraction was attained at 6 hr while that of all other tissue fractions peaked at 16 hr after carcinogen feeding. The specific activity of those tissue fractions containing the smaller percentage of total lipid (mammary teat and vascular area) was less than, but the same pattern as, those fractions containing the greater percentage of total lipid (perirenal fat, mammary fat pad, and isolated mammary fat cells). However, a concomitant increase in the specific activity of the parenchymal cells did not occur while the specific activity of the isolated mammary fat cells was decreasing. The pattern of total parenchymal cell specific activity was almost identical with that of the parenchymal cell intracellular lipid although the values were much lower. While the parenchymal cell intracellular lipid reached a peak uptake and began to decline rapidly, the lipid-extracted parenchymal cell specific activity continued to rise. During the rapid decrease in intracellular lipid specific activity, the lipid-extracted parenchymal cells reached a peak and then apparently leveled off. These data suggested that the concentration of the carcinogen in mammary adipose tissue obscured the uptake of the carcinogen by mammary parenchymal cells because of the lipid solubility of the compound. Furthermore, since the uptake of the carcinogen by the mammary parenchymal cells and fat cells occurred simultaneously and independently, it was apparent that mammary fat cells were of minor importance in the uptake of the carcinogen by mammary parenchymal cells. These data also indicated that the carcinogen was first concentrated in the intracellular lipid of the parenchymal cell and released to other cellular constituents. The dimethylbenzanthracene released from the parenchymal cell intracellular lipid was apparently firmly bound by some cellular component and the level of bound dimethylbenzanthracene was maintained by a continued release from intracellular parenchymal cell lipid.