Influence of age and gland topography on cell kinetics of normal human breast tissue

It has been determined in experimental animal models that the susceptibility of the mammary gland to chemically induced carcinogenesis is directly related to the rate of cell proliferation of the gland at the time of carcinogen exposure and inversely related to its degree of differentiation. Cell proliferation, in turn, depends on the topographic location of cells within the mammary gland tree and is modulated by age, among other factors. To determine whether age and gland topography similarly influence cell kinetic parameters in the breast of human females, the following study was done. Fifteen samples of normal human breast tissue were obtained from areas adjacent to histopathologically proved benign lesions. Tissue fragments were incubated in organ culture dishes containing [3H]thymidine ([3H]dThd) and processed for DNA labeling index (DNA-LI), length of cell cycle (Tc), and growth fraction (GF) determination; double labeling with [3H]dThd and [14C]thymidine was used for length of the S-phase determination. The mean values obtained revealed that both DNA-LI and GF were lower, with a concomitant lengthening of G1 and Tc in older women than in young women. The correlation of these values with the gland's topography revealed that in both young and older women, the highest GF and DNA-LI were observed in intralobular terminal ducts, decreasing in alveoli and ducts.