Shuneki Shoji

Formal genesis of the outflow tracts of the heart revisited: previous works in the light of recent observations.

The formal genesis of the great arteries continues to be controversial due to the lack of consensus of septation of the developing outflow tract. In order to make it clear how the great arteries are generated, we have re‐examined our previous papers which emphasized the formation of the aorta and pulmonary trunk, concept of the aorticopulmonary septum, formation of the leaflets of semilunar valves, morphogenesis of the crista supraventricularis, programmed cell death and rotation of the outflow tract. In the present paper, we compare outcomes gained from the re‐examination of our previous papers with prevalent interpretations of the arterial trunk. We obtained conclusions as follows: (i) The elongation of the fourth and sixth aortic arch arteries, which sprout from the wall of the aortic sac at the expense of the distal truncus, contributes to the formation of the aorta and pulmonary trunk; (ii) Smooth muscle cells of the tunica media of the arterial trunks do not arise from the transformation of the myocardial cells of the truncus wall (not ‘arterialization’); (iii) Truncus swellings are divided into two parts: distal and proximal. The former contributes to the separation of the orifices of arterial trunks (‘aorticopulmonary septum’). The latter contributes to the formation of the leaflets of the semilunar valves of the aorta and pulmonary trunk; (iv) The origin of the myocardial cells of the crista supraventricularis is a wall of the conus originated from secondary/anterior heart fields; and (v) There has been no acceptable proof that rotation and counterclockwise rotation are involved.

Inhibitory action of (-)-epigallocatechin gallate on radiation-induced mouse oncogenic transformation.

The anticarcinogenic activity of a major component of green tea, (-) epigallocatechin gallate (EGCg) was examined by using the radiation-induced oncogenic transformation in C3H10T1/2 cells. EGCg substantially suppressed the radiation-induced transformation so that the transformation frequency with 15 microM of EGCg was reduced nearly to spontaneous levels. This effect of EGCg was in a dose-dependent manner and significant suppression of transformation was observed even in treatment of cells with 5 microM of EGCg concentration where the cytotoxicity was mild. The inhibitory effect of EGCg was maximal when it was present during the entire incubation period. However, neither treatment prior to nor concurrent with radiation was effective, suggesting that EGCg action is mainly involved in the promotional stage of C3H10T1/2 cell transformation.

Gastric tumor induction by 1,2-dimethylhydrazine in Wistar rats with intestinal metaplasia caused by X-irradiation

Five‐week‐old male Wistar rats were X‐irradiated with a total of 20 Gy in 2 equal fractions at a 3‐day interval. 1,2‐Dimethylhydrazine (DMH) solution was injected i.m. into the back musculature at a dose of 20 mg/kg body weight weekly for 10 weeks, beginning 20 weeks after the final irradiation. Twelve months after the initial carcinogen treatment, tumors in the fundus of the glandular stomach were observed in 5 of 23 animals receiving both X‐irradiation and DMH treatment. No tumors of the glandular stomach were observed in the DMH and X‐ray alone or nontreatment groups. It is concluded that the presence of intestinal metaplasia may increase sensitivity to the induction of gastric tumors by carcinogens like DMH.

Developmental malformations and intrauterine deaths in gamma-ray-irradiated scid mouse embryos.

PURPOSE To examine the induction by radiation of developmental malformations and intrauterine deaths in severe combined immunodeficiency (scid) mice. MATERIALS AND METHODS The scid embryos, as well as those of C.B-17 control mice, were irradiated with graded doses of 60Co gamma-rays on gestation day 8. RESULTS Intrauterine deaths in scid mice increased with radiation dose, and their frequency was substantially higher than in C.B-17 mice. The LD50 for intrauterine death in scid mice was 0.58 Gy and 1.25 Gy in C.B-17 mice. In addition, after irradiation scid mice showed several types of developmental malformations, including meningoencephalocele, spina bifida, eye defects, tail defects and oedema. Malformation incidences were higher in scid than in C.B-17 mice: 33.3% in scid mice irradiated with 0.75 Gy and 13.0% in C.B-17 mice irradiated with 1.0 Gy. However, when malformation incidences were plotted against intrauterine deaths, all the data, irrespective of the type of mouse, essentially fell along a single straight line. CONCLUSIONS These results suggest that some mechanism common to both scid and normal mice induces developmental malformations. This mechanism involves cell killing. Residual DNA damage, such as double-strand breaks, could be associated with radiation-induced teratogenesis.