Simultaneous induction of mutagenic and cancerogenic effects in T × HT mice with transplacental ethylnitrosourea treatment

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Abstract
The relationship between mutagenesis and carcinogenesis was investigated in T × 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 < 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.

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