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.