The Neoplastic Potentialities of Mouse Embryo Tissues

Abstract

In previous papers from this laboratory (1) experiments have been described which were made to learn how soon in the life of the organism cells possess the ability to become tumor cells. The neoplastic potentialities of various mouse embryo tissues, procured in the latter half of gestation, were tested by transplanting them to adults, together with methylcholanthrene. Tumors arose swiftly and in great diversity, yet it was questionable whether the cells exposed to the carcinogen were still in the embryonic state when they underwent neoplastic change, since the interval before the growths first became perceptible somewhat exceeded the time until birth, had the embryos been left undisturbed. If it had been possible to utilize the cells of very young embryos perhaps tumors could have been obtained within this period, but they did not survive the requisite exposure to methylcholanthrene, even when this was circumspectly injected into the "beads" along the uterus. Obviously for a decisive test of the neoplastic potentialities of embryo cells these must be exposed in utero to a carcinogen acting so speedily that its neoplastic effects will be evident almost at once. Recent authors who have produced pathological changes in mouse embryos with the Roentgen rays (2) have made no mention of tumor formation, and the polycylic hydrocarbons fail to pass the placenta in effective quantity. It was recalled however that the injection of the highly diffusible hypnotic, urethane, into adult mice of strains liable to pulmonary adenomas in old age causes these growths to appear earlier than usual and in much greater number (3). We had employed such a strain of animals when testing with methylcholanthrene the neoplastic potentialities of transplanted fragments of embryo lung, and had noted that multiple adenomas formed within 2 to 3 weeks (4). Consequently urethane was now injected repeatedly into pregnant females, and their offspring were searched for adenomas. These were sometimes visible in 3-day-old animals, and often had attained a considerable size within 10 days, none appearing in controls. The urethane could have acted in utero for only a few hours, and it produced no visible damage in the lungs of

Nuclear Receptor Expression and Function in Human Lung Cancer Pathogenesis

“…Although diverse animal models, including a genetic and chemical carcinogen models mimicking smoking, have been extensively utilized for genetic or epigenetic studies of lung cancer, understanding oncogenesis in human lungs remains as a concern [ 41 – 43 ]. In this regard, we believe that this panel could represent the first human pathogenesis model to study genetic as well as environmental causes (e.g.…”

In Utero Phase Carcinogenicity Testing

“…Two early studies of the influence of transplacental exposure to carcinogens (Larsen, 1947;Smith & Rous, 1948) reported that the administration of urethane to pregnant female mice accelerated the rate of deve lopm ent and number of lung tumors in their offs pr ing. Lars en (1947) reported that the intraperitoneal injection of pregnant Strain A fem ale mice at tim e intervals ranging fr om 1 to 5 days prepartum r es ulted in an s tatis tically s ign if ican t incr eas ed inciden ce of lu ng tumors com pared with postpartum exposure beginning at adolescence.…”

Tumors in Two Generations of Mice in Different Environmental Conditions

“…Reports of such investigations first appeared in literature in the late 1940s. It was demonstrated by Larson that pul monary tumors are induced transplacentally in mice by urethane [2], Smith and Rous studied the effect of urethane in the young after injecting pregnant mice from the 12th to the 18th day of gestation [3]. The offspring were autopsied at 3, 10, or 60 to 70 days of age.…”