Tumor phenotype and susceptibility to progression as an expression of subpopulations of initiated murine cells.
Currently, it is conceived that a number of events, or hits, are required for the induction of tumors by chemical agents. The first phase of this sequence, initiation, is considered to result from at least one event in the genetic apparatus. Analyses of this sequence, however, usually give little consideration to the nature of the target cell or to the characteristics of the resultant tumors. Vesselinovitch et al. (Cancer Res., 38: 2003-2010, 1978) have reported that a single, small pulse of carcinogen can induce early and numerous liver tumors when administered neonatally to mice with a genetic predisposition to hepatotumorigenesis. In the current study, the nonpredisposed strain C57BL/6N was also shown to be highly susceptible to diethylnitrosamine during the neonatal period. C57BL/6N demonstrated large numbers of two of the three types of liver tumors seen in livers of genetically predisposed mice, one of which required the additional stimulus of dietary phenobarbital for growth. Tumors of more malignant phenotype were demonstrated only in genetically predisposed mice (C57BL/6N X C3H/HeN F1) that received one dose of carcinogen. These findings suggest that the phenotype of a tumor that results from a pulse of a chemical carcinogen may depend upon the target cell. The initiated cells that result from this hit may vary from those that demonstrate very little progression in cell type and may or may not require exogenous enhancement of growth to those that can progress very rapidly to fully malignant behavior. The latter might arise from a hit in a genetically initiated cell, the result of which is a more rapid progression in tumor type.
Becker
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D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D004052:Diethylnitrosamine / Q000494:pharmacology; D004198:Disease Susceptibility; D004347:Drug Interactions; D005260:Female; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010634:Phenobarbital / Q000494:pharmacology; D010641:Phenotype; D011247:Pregnancy; D013997:Time Factors; D000509:alpha-Fetoproteins / Q000032:analysis
D000509:alpha-Fetoproteins; D004052:Diethylnitrosamine; D010634:Phenobarbital