Abstract
It is hypothesized that stem cells are the targets for carcinogenesis. If cancer arises from stem cells, cancer risk would depend on population size and susceptibility to carcinogens of stem cells . Study on A-bomb survivors shows clear age-related decline in the susceptibility to radiation-induced breast cancer. It is also known that women who undergo full-term pregnancy have a reduced lifetime risk of breast cancer. These results suggest that protection results from intrinsic effect of aging and parity on breast tissues. We here examined change in the biological characteristics of rat mammary stem cells (clonogens) with aging and parity. The results are as follows. (1) Total numbers of clonogens increased exponentially with a population doubling time of 4 days during pre-pubertal period. After puberty, it lengthened to 30 days. The total number of clonogens in abdominal and inguinal mammary glands of 2 week-old rats was 200, while that in 8 week-old and thereafter was more than 5,000. (2) The number of mammary clonogens in rats which underwent pregnancy was less than 500, while that of nulliparous rats was 6,000. (3) Prolactin treatment increased clonogen number by 8 folds in 8 week-old rats whereas it increased by just 2 folds in one year-old rats. (4) The surviving fraction of clonogens before puberty after 5 Gy was 0.1, while it was 0.3 after puberty. These results suggest that population size, response to prolactin and radiobiological characteristics of clonogens, which change in age- and parity-dependent fashion, is associated with susceptibility to radiation-induced mammary tumors. [J Physiol Sci. 2006;56 Suppl:S13]
