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 microns 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 greater than 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.
Yang
D
D
Department of Microbiology, Michigan State University, East Lansing 48824-1316.
Louden
C
C
Reinhold
D S
DS
Kohler
S K
SK
Maher
V M
VM
McCormick
J J
JJ
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D005347:Fibroblasts; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans
D006133:Growth Substances; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D002118:Calcium