Can prenatal X-irradiation in mice act as an initiator stimulus in a modified 2-stage Berenblum/Mottram experiment with postnatal promotion with phorbol ester TPA?

Long-term animal experiments with prenatally X-irradiated offspring have so far not unequivocally settled the question of elevated tumor susceptibility. We have pursued this problem further in a modified 2-stage carcinogenesis-Berenblum/Mottram experiment. Prenatal X-irradiation of mice has thus been regarded as a possible initiator stimulus, with a postnatal promotion stimulus being given by applying the phorbol ester TPA to the offsprings' skin. This treatment has, however, not produced a higher tumor yield, neither of the skin nor of the internal organs, than that produced by X-irradiation in utero alone. This failure seems partly due to the dysplastic nature of the epidermis of prenatally X-irradiated mice, which also fails to respond to TPA application by way of hyperplasia or by an increased inflammation tendency and ulcer formation. We suggest that a decrease in prostaglandin synthesis after prenatal X-irradiation is an important factor for the unchanged tumor susceptibility, especially of the skin.