Independent expression of chemical carcinogen-induced phenotypic properties frequently associated with the neoplastic state in a cultured guinea pig cell line.
Relationships among carcinogen-induced morphlogic transformation, anchorage independence, susceptibility to growth inhibition by the immunologic hormone lymphotoxin and to natural killer cell and natural lymphoid cell cytotoxicity, natural delayed-type (tuberculin) skin reactivity, and tumorigenicity were investigated with the use of a guinea pig cell culture model of carcinogenesis characterized by sequential, extended developmental stages. Twelve cultures of passage 90 nontumorigenic fibroblast-like line 118 cells derived from a 36-day-old strain 2/N guinea pig fetus were treated with 10 micrograms benzo[a]pyrene or 1 microgram N-nitroso-N-methylnitroguanidine/ml medium for 3 days and maintained in exponential growth. One week later, all cultures exhibited morphologic alteration, and by 8 weeks two-thirds exhibited morphologic transformation. After 4 months, morphologically altered or transformed cells expressed progrssive colony growth in semisolid 0.35% agar medium. Susceptibility to lymphotoxin colony inhibitory activity developed subsequent to morphologic transformation but independently of growth in semisolid medium. Susceptibility to natural lymphoid cell destruction was also independent of growth in semisolid medium. All four phenotypic properties were expressed only after carcinogen treatment and 12 months later remained unaccompanied by either natural delayed-type skin reactivity or by the ability of the cells to grow as tumors in syngeneic guinea pigs of nu/nu mude mice. Thus while morphologic transformation, colony formation in semisolid medium, and susceptibility to lymphotoxin and to nautral lymphoid cell cytotoxicity were frequently associated with neoplasia, they could be expressed independently of one another; individually or collectively in a specific developmental sequence, they were insufficient for expression of either natural delayed-type skin reactivity of tumorigenicity.
D000818:Animals; D001580:Benzopyrenes; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000473:pathology*; D003114:Colony-Forming Units Assay; D006168:Guinea Pigs; D008297:Male; D008769:Methylnitronitrosoguanidine; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000139:chemically induced; D010641:Phenotype
D001580:Benzopyrenes; D008769:Methylnitronitrosoguanidine