PuSH - Publication Server of Helmholtz Zentrum München: Sequence-dependent toxicity and small bowel mucosal injury in neonatal mice, treated with low doses of 5-Azacytidine and X-irradiation at the late organogenesis stage.

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Schmahl, W.G.

Sequence-dependent toxicity and small bowel mucosal injury in neonatal mice, treated with low doses of 5-Azacytidine and X-irradiation at the late organogenesis stage.

Radiat. Environ. Biophys. 21, 235-245 (1983)

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A combined treatment of pregnant mice on day 12 of gestation with both azacytidine and X-irradiation in low doses induces sequence-dependent histological effects. These effects, in turn, induce different symptomatic signs if evaluated either prenatally or neonatally. In the azacytidine treatment/X-irradiation sequence the malformations of the fetal forebrain are predominant. Consequently, these dams show a high incidence in the stillbirth rate. Conversely, the X-irradiation/azacytidine treatment schedule leads only to a mild brain hypoplasia, and does not cause an increased stillbirth rate. In these offspring, however, a severe impairment of small bowel epithelial proliferation capacity was found. This is linked to an outstanding neonatal mortality within 48 h after birth. The pathogenesis of these sequence-dependent effects can be attributed to a selective vulnerability of cells in different stages of the generation cycle. This comprises a high degree of cytolethality affecting the S/G2-stage cells in azacytidine/X-irradiation treatment and the G1/S-stage cells in the reverse combinations (Schmahl 1979). The present observations show the validity of a teratological assay in providing a detailed analysis of the cell kinetic responses after combined noxious influences.

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