Studies on the mode of action of chemical carcinogens in cultured mammalian cells

Conference · Thu Jan 01 04:00:00 EST 1981

OSTI ID:5294306

Jones, C; Huberman, E

It has been shown that most carcinogens require metabolic activation to electrophilic reactants prior to exerting their toxic effects. Such reactive metabolites are capable of binding to cellular macromolecules including DNA, suggesting the production of critical mutations as the initial event in the process of tumor development. Indeed most chemical carcinogens have been shown to act as mutagens as well. For an accurate assessment of the genetic risk from exposure to these chemicals, it is not sufficient to merely indicate mutagenic potential. It must be shown that a quantitative relationship exists between carcinogenicity and mutagenicity and that the same metabolites are responsible in both cases. In order to make a valid extrapolation from the in vitro systems to man, one must devise systems which should also take into account the organ and/or species specificity of the carcinogens. Some classes of chemicals do not appear to act via a mutational mechanism and yet can influence the development of tumors. These chemicals are thought to act subsequent to an initiation event caused by another chemical and amplify or promote the development of tumors. It would be useful to devise simple in vitro systems in which both the identity and mode of action of such chemicals can be investigated. The results obtained from such an approach and the conclusions drawn from these studies are discussed. It was found that the human cell lines, HL-60 and HO melanoma, may offer a useful model for studying the mode of action of certain classes of tumor promoters and in evaluating some unknown chemicals for this activity. The cell-mediated mutagenesis assays enable the mutagenic and hence possibly, the initiating activity of a chemical to be investigated, whereas specific alterations in the growth and cell differentiation of human cells such as the HL-60 myeloid cells produced by a chemical may be indicative of a tumor-promoting potential. (ERB)

• Research Organization: Oak Ridge National Lab., TN (USA)
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 5294306
• Report Number(s): CONF-8103119-2; ON: DE82008826
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
BIOLOGICAL EFFECTS
BIOLOGICAL MODELS
CARCINOGENESIS
CARCINOGENS
CELL CULTURES
CELL DIFFERENTIATION
IN VITRO
METABOLIC ACTIVATION
MUTAGENESIS
MUTATIONS
PATHOGENESIS
PROMOTERS
TUMOR PROMOTERS