Malignant transformation of diploid human fibroblasts by transfection of oncogenes: Progress report, July 1986--June 1989

Technical Report · Sun Jan 01 04:00:00 EST 1989

DOI:https://doi.org/10.2172/6067022· OSTI ID:6067022

McCormick, J. J.; Maher, V. M.

Although there is good evidence that carcinogen exposure is a major cause of human cancer, it has proven impossible to transform normal human fibroblasts or epithelial cells in culture into malignant cells by treating them with carcinogens. This failure may reflect an inability to identify and isolate cells containing one or more premalignant changes so that these can be expanded and exposed to carcinogens a second time to induce additional required changes. A second serious roadblock to the sequential introduction of changes and expansion of clonally-derived cells containing such premalignant changes in the finite life span of human cells in culture. Using transfection of specific human oncogenes in a series of specially-selected vectors, we have overcome these obstacles and have recently succeeded in generating an infinite life span diploid human cell strain MSU-1.0, which appears to be normal in all other characteristics. From that cell a second cell strain, MSU-1.1, was generated which we have been able to transform into a malignant state not only by transfecting the cells with oncogenes but also by treating them with chemical carcinogens. We now have evidence that there is not just a single linear process which results in malignant transformation. Rather, cells appear to progress to malignancy on a series of parallel, sometimes overlapping tracks. We now propose to carry out detailed studies of the specific mechanisms of malignant cell transformation using the cell strains available in this laboratory to achieve the goal of building relevant quantitative models of carcinogenesis. 29 refs.

• Research Organization: Michigan State Univ., East Lansing (USA). Carcinogenesis Lab.
• DOE Contract Number: FG02-87ER60524
• OSTI ID: 6067022
• Report Number(s): DOE/ER/60524-3; ON: DE89013966
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
CARCINOGENESIS
CELL PROLIFERATION
CELL TRANSFORMATIONS
CONNECTIVE TISSUE CELLS
DNA
DOCUMENT TYPES
FIBROBLASTS
GROWTH FACTORS
MAMMALS
MAN
MITOGENS
MOLECULAR BIOLOGY
MUTAGENESIS
NUCLEIC ACIDS
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
PATHOGENESIS
PRIMATES
PROGRESS REPORT
PROTEINS
SOMATIC CELLS
VERTEBRATES