Requirement of long progression time for the expression of neoplastic phenotypes following direct perturbation to specific region(s) of DNA of Syrian hamster embryo cells.
We have studied the neoplastic transformation of early passage Syrian hamster embryo cells in culture, which were initiated by a specific perturbation of DNA replicated during different periods of S phase. The cells were treated with a "1-h pulse" of 5-bromodeoxyuridine (BrdUrd), followed by a "5-min" irradiation with near ultraviolet (near UV) light. The treated cells were successively subcultured and tested for growth in soft agar and tumorigenicity in newborn hamsters. Neoplastic transformation was induced by treatment with BrdUrd followed by near UV irradiation within the first 4 h of S phase, which was 5 h in duration. Cells treated with BrdUrd plus near UV irradiation during late S phase (the last hour) or during the absence of DNA synthesis (outside of the S phase) were not transformed. In addition, cultures treated in either G1, G2, or S phase with BrdUrd alone or with near UV alone also were not transformed. While morphological transformation, somatic mutation, and DNA and chromosomal aberrations can be observed either immediately or after a few cell divisions, 100 to 200 population doublings after the treatment were required for the emergence of a neoplastic subpopulation, as measured by anchorage independent growth and tumorigenicity. Furthermore, cellular DNA replicated during the first 4 h of S phase is sensitive to the perturbation which leads to neoplastic transformation. These results indicate that the direct perturbation of specific region(s) of cellular DNA can initiate the neoplastic transformation process; but for full expression of the neoplastic phenotypes, a long progression time is required for the acquisition of anchorage-independent growth and tumorigenicity.
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D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D002478:Cells, Cultured; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D066298:In Vitro Techniques; D007621:Karyotyping; D009154:Mutation / Q000187:drug effects; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D013997:Time Factors; D014466:Ultraviolet Rays
D004247:DNA; D001973:Bromodeoxyuridine