MALIGNANT TRANSFORMATION OF HUMAN FIBROBLAST CELL STRAIN MSU-1.1 BY (+/-)-7-BETA,8-ALPHA-DIHYDROXY-9-ALPHA,10-ALPHA-EPOXY-7,8,9,10-TETRAHYDROBENZO[A]PYRENE

Treatment of MSU-1.1 cells, a near-diploid, karyotypically stable, infinite life-span human fibroblast strain, with (+/-)-7-beta,8-alpha-dihydroxy-9-alpha,10-alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene induced focus formation. Eight independent foci were isolated and the cell strains developed from them were examined for characteristics of malignant cells. Each grew to a higher density in medium containing 1% serum than did the MSU-1.1 cells. Three of the eight grew rapidly in serum-free medium without added growth factors, formed colonies in agarose with diameters of greater-than-or-equal-to 120-mu-m at a frequency of 5-19%, exhibited loss of genetic material, and, when injected into athymic mice, formed sarcomas that reached 6 mm in diameter within 2-3 wk. One produced high-grade sarcomas (progressively growing, invasive tumors exhibiting high mitotic activity); the other two produced low-grade sarcomas (tumors with a lower degree of mitotic activity) that developed focal areas of high-grade malignant cells if left in the animals for > 4 wk. A fourth cell strain formed high-grade sarcomas only after 2.5-3 mo, but the tumor-derived cells analyzed showed the same growth properties as the three malignant cell strains described above, exhibited loss of genetic material, and, when reinjected into athymic mice, produced high-grade sarcomas with a short latency period.