Growth Inhibition of Estrogen-Sensitive Tumor Cells in Newborn Rats. Probable Role of Alpha-Fetoprotein2

Publisher Website
Google Scholar
Abstract
Growth rates of 2 rat pituitary tumor cells in intact WF rats of different ages and in different culture conditions were compared. One of the tumor cell lines, C29RAP, was estrogen (E)-sensitive (grows faster in intact females and E-inoculated hosts than in WF males or castrated females). The other tumor, MtT/F4 (F4), was autonomous (grows at a similar rate in isogenic F344 rats regardless of their sex and E-levels). The 2 tumors and the cells growing in culture had comparable amounts and intracellular distribution of 17β-estradiol (E2) receptors. The ages of the hosts at which the C29RAP cells were injected did not affect the E-sensitive growth pattern. The latency period before tumor appearance was considerably longer, however, when C29RAP cells were injected into 1- and 10-day-old rats as compared with that seen in adult hosts. This effect was common to males and females. The injection of E for 30 days shortened the latency period in newborn hosts and cancelled the sex-dependent difference in the growth rate. Similar experiments done with F4 tumor cells did not show a delayed growth effect in newborn F344 rats. Experiments conducted in cultures with the use of media supplemented with sera from rats of different ages [fetus (FRS); 1-, 10-, 20-, 30-, and 45-day-old rats; and adult (>90-day-old) rats] indicated that sera from younger rats (1- and 10-day-old) and FRS contained elements that arrest the growth of C29RAP cells. This in culture condition is similar to that obtained in animals. When supplemented to media, sera from Morris hepatoma 7777-bearing rats had the same effect on C29RAP cells as did FRS or sera from 1-day-old rats. When supplemented to media, sera from hepatoma 7787-bearing rats had the same effect on C29RAP cells as did adult rat serum. The concentration of alpha-fetoprotein (AFP) in FRS was about 7.80±1.50 mg/ml, whereas the concentration of AFP in hepatoma 7777-bearing rats was about 12.00±1.80 mg/ml. F4C1 cells, derived from F4 tumors, were not adversely affected by the different sera-supplemented media listed earlier. These results suggested that 1) the presence of E2 receptors may be necessary but not sufficient to qualify cells to be considered E2-sensitlve, 2) the experiments related were an effective example for a selective approach to the isolation and characterization of bona fide E2-sensitive cells, 3) E2-sensitive tumor cells may be delayed in expressing their malignant growth properties if injected into hosts during the perinatal period, and 4) AFP may be the factor that prevents the growth of E2-sensitive tumor cells during the perinatal stage.