Genetic forms of neoplasia in man: a model for the study of tumor promotion in vitro.
In the studies described here, we demonstrated a unique dose-response (concaved upward) to TPA in sparse human cell cultures and a dose-dependent stimulation of cell proliferation in confluent cultures, suggesting a functional difference in putative TPA receptors between these two conditions. This bimodal dose-response to TPA was not seen in sparse cultures of established normal rodent cell lines. The phenotypic profile of ACR cells chronically exposed to TPA, although effecting a change toward a more transformed phenotype (e.g., growth in agar), was in large measure neither stable nor uniform during consecutive passages or for a given cell strain during different periods of TPA application. ACR cells when exposed to TPA alone appear to grow in the anterior chamber of the eye of a nude mouse. We speculated that TPA-induced aneuploidy in these cells, coupled with DNA instability and aberrant chromosomal segregation, may conceivably be consistent with neoplasia in initiated ACR cells. Finally, the apparent susceptibility of ACR cells to further transformation by TPA and N-methyl-N1-nitro-N-nitrosoguanidine (MNNG) (34,48) and by ocongenic viruses (37,45) indicates that genetic information residing within these cells, probably in the form of an ACR mutation, renders them more sensitive to these two distinct classes of carcinogens.
D000236:Adenoma / Q000235:genetics; D001647:Bile Acids and Salts / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D003043:Cocarcinogenesis; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics; D009154:Mutation; D010704:Phorbols / Q000494:pharmacology*; D012867:Skin; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D001647:Bile Acids and Salts; D010704:Phorbols; D004247:DNA; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine