Malignant transformation of human fibroblasts in vitro

Conference · Tue Jan 01 04:00:00 EST 1991

OSTI ID:6827277

McCormick, J J; Maher, V M

Although carcinogens cause human tumors, human cells in culture have not been successfully transformed to malignancy by exposure to carcinogens. It is now recognized that malignant transformation involves multiple changes within a cell and, therefore, successive clonal selection of cells containing such changes must occur. One explanation for the failure to induce in vitro malignant transformation of human cells could be inability to recognize cells that have undergone intermediate changes so as to expand the population, expose the cells a second time, cause further changes, etc. therefore, we transfected finite life span diploid human fibroblists with oncogenes known to be active in cells derived from human fibrosarcomas or effective in transforming animal fibroblasts to determine the phenotypes they produced. Transfection of a sis gene, or an H-, or H-ras oncogene caused the cells to acquire many characteristics of malignant cells, but not to acquire an infinite lift span or become malignant. We recently succeeded in developing an infinite life span human fibroblasts cell strain, designated MSU-1.1, which has a stable, near-diploid karyotype, composed of 45 chromosomes including two marker chromosomes. We have shown-that these cells can be transformed to malignancy by transfection of the H-, K-, or N-ras or the v-fes oncogene. All of the malignant H-, K-, or N-ras transfected derivatives examined have exhibited the stable karyotype of the parental MSU-1.1 cells. We have also found rare spontaneous clonal variants of MSU-1.1 that are malignantly transformed and have shown that malignant variants can also be induced by carcinogen treatment.

• Research Organization: Michigan State Univ., East Lansing, MI (United States). Carcinogenesis Lab.
• Sponsoring Organization: DOE; DOHHS; USDOE, Washington, DC (United States); Department of Health and Human Services, Washington, DC (United States)
• DOE Contract Number: FG02-87ER60524
• OSTI ID: 6827277
• Report Number(s): CONF-9101158-1; ON: DE93005929; CNN: CA21289; ES65152
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
550900 -- Pathology
560120 -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
560300 -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
CELL TRANSFORMATIONS
CLONING
CONNECTIVE TISSUE CELLS
DNA HYBRIDIZATION
DNA-CLONING
FIBROBLASTS
GENES
HYBRIDIZATION
MOLECULAR BIOLOGY
ONCOGENES
ONCOGENIC TRANSFORMATIONS
SOMATIC CELLS