Predominance of a cell population less sensitive to carcinogenesis in neoplastic cells of 3-methylcholanthrene-induced tumors in mouse aggregation chimeras.
Tumors were induced by i.m. injections of 3-methylcholanthrene (0.5 mg) in 100% experimental aggregation chimeras derived from two mouse strains C57Bl/6J (hereafter called B6) and A/J, dimorphic for the enzyme glucosephosphate isomerase (Gpi-1a or Gpi-1b) and differing in coat color, aryl hydrocarbon hydroxylase inducibility, and cytotoxic activities of natural killer cells and macrophages. In the majority of host tissues and organs, such as coat, lung, spleen, and skeletal muscle, the B6 phenotype was predominant. Likewise, the nonneoplastic intratumoral host cells of both induced primary tumors and parental tumor transplants in chimeras were of B6 origin. In contrast, neoplastic cells in 70% of the tumors originated exclusively from the less aryl hydrocarbon hydroxylase-inducible and less immune competent A/J strain. The A/J origin was verified by subsequent cell culturing of the tumors. Only 30% of the tumors contained neoplastic cells of both A/J and B6 phenotype. A further reduction of mixed tumors was achieved with lower doses (0.1 and 0.06 mg) of the carcinogen. The dominance of the A/J phenotype of the tumors contrasted not only with aryl hydrocarbon hydroxylase inducibility and host cell composition but also with tumor pathogenesis (at 0.5 mg 3-methylcholanthrene) in the parental strain. Whereas tumor incidence was 100% in the B6 strain, it was only 65% in A/J mice, with tumors also developing later. As the in vivo and in vitro growth rates of parental strain-derived tumors were comparable, a cell selection caused by different growth rates favoring the A/J phenotype appeared unlikely.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002678:Chimera; D004790:Enzyme Induction; D005260:Female; D008297:Male; D008748:Methylcholanthrene; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
D008748:Methylcholanthrene; D001189:Aryl Hydrocarbon Hydroxylases