Simultaneous induction of mutagenic and cancerogenic effects in T x HT mice with transplacental ethylnitrosourea treatment.
The relationship between mutagenesis and carcinogenesis was investigated in T x HT crossbred mice using diaplacental application of ethylnitrosourea (ENU) at different stages of embryonal development. Mutagenesis was detected by induction of coat color spots, and the carcinogenic response was investigated in a long-term follow-up study of the F1-generation. The animals were particularly sensitive to induction of tumors at the central nervous system (CNS)-skull/vertebra interface (30% and 20% in ENU-treated male and female offspring, respectively, compared with less than 1% in controls). There was a correlation between the appearance of these tumors and the presence of color spots. This correlation was low but statistically significant in female offspring. Three other types of tumors showed a correlation with the presence of coat color spots. Liver tumors were significantly increased in color spot-positive females but unchanged in males. Lung tumors were reduced in color spot-positive males and appeared earlier in color spot-positive females. There was a lower incidence of lymphoma/leukemia in all spot-positive mice. The reduction in tumor incidence beyond the spontaneous rate in spot-positive animals might be caused by a high cytolethal response to ENU in the relevant organs and tissues.
Schmahl
W
W
Institut für Pathologie, Gesellschaft für Strahlen- und Umweltforschung mbH München, Neuherberg, Federal Republic of Germany.
Neuhäuser-Klaus
A
A
Leierseder-Bauer
M
M
Luz
A
A
D000818:Animals; D002273:Carcinogens; D005038:Ethylnitrosourea / Q000633:toxicity*; D005260:Female; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D009030:Mosaicism; D009153:Mutagens; D009154:Mutation; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D011247:Pregnancy
D002273:Carcinogens; D009153:Mutagens; D005038:Ethylnitrosourea