Multiparametric evaluation of the toxic responses of normal human cells treated in vitro with different classes of environmental toxicants.

  title={Multiparametric evaluation of the toxic responses of normal human cells treated in vitro with different classes of environmental toxicants.},
  author={Lawrence E. Allred and James W. Oldham and George E. Milo and O R Kindig and Charles C. Capen},
  journal={Journal of toxicology and environmental health},
  volume={10 1},
Eight compounds representing three classes of chemicals were evaluated for their toxic effects on normal neonatal human foreskin fibroblasts in vitro. A battery of toxicity assays was employed to measure the effects of the chemicals on cell viability, DNA synthesis, protein synthesis, DNA repair synthesis, cell ultrastructure, membrane-bound and soluble cytoplasmic proteins, and the activities of six enzymes: beta-glucuronidase, acid phosphatase, gamma-glutamyl transpeptidase, alkaline… 
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Toxicity Tests with Mammalian Cell Cultures
Cell culture can be used to screen for toxicity both by estimation of the basal functions of the cell (i.e. those processes common to all types of cells) or by tests on specialized cell functions
Human neonatal keratinocytes have very high levels of cellular vitamin A-binding proteins.
The levels of CRABP were much lower in the foreskin dermis than in the epidermis and the levels measured in the fibroblasts cultured from this dermis were consistent with the dermal levels, suggesting that another dermal cell type has high levels of CRBP.
A conundrum in molecular toxicology: Molecular and biological changes during neoplastic transformation of human cells
Historically, this work has assumed only a limited role for epigenetic modulation of molecular changes that occur during progression; however, the data suggest quite strongly that nonmalignant tumor populations can be converted to a more malignant phenotype without additional mutations taking place and, conversely, malignant populationsCan be downregulated to a nontumorigenic phenotype.
Conditions for transformation of human fibroblast cells: an overview.
Criteria can be established to measure the expression of progression of these carcinogen initiated cells towards a malignant phenotype and there is little evidence to suggest that these abnormal phenotypes exhibit an infinite lifespan using the selection pressures for isolation of the transformed phenotypes.


The toxicological evaluation of the mycotoxins T-2 and T-2 tetraol using normal human fibroblasts in vitro.
Normal human fibroblasts in vitro were used as a system to examine the cellular effects of potentially toxic compounds and multiple biochemical parameters with ultrastructural and cytotoxicity studies were effective in demonstrating the mechanisms as well as the degree of toxicity induced by these chemical compounds.
Cell culture as a test system for toxicity
  • S. Metcalfe
  • Biology, Medicine
    The Journal of pharmacy and pharmacology
  • 1971
It is suggested that the ability of the food additive butylated hydroxytoluene to act as a potent inhibitor of cellular growth may account for its reported ability to prolong the life span of mice.
Effect of DNA repair on the cytotoxicity and mutagenicity of polycyclic hydrocarbon derivatives in normal and xeroderma pigmentosum human fibroblasts.
Evidence was obtained that cells from an XP variant patient are abnormally susceptible to mutations induced by hydrocarbon epoxides and, as is the case following exposure to UV, are abnormably slow in converting low molecular weight DNA, synthesized from a template following Exposure to hydrocarbonEpoxides, into large-size DNA.
Biochemical activation of aryl hydrocarbon hydroxylase activity, cellular distribution of polynuclear hydrocarbon metabolites, and DNA damage by polynuclear hydrocarbon products in human cells in vitro.
It was concluded that benzo(a)pyrene can initiate all the biochemical events in human cells probably necessary to initiate transformation of human cells in vitro.
Mutagenicity to mammalian cells of epoxides and other derivatives of polycyclic hydrocarbons.
It is demonstrated that metabolic activation of polycyclic hydrocarbon is required for mutagenic activity in mammalian cells.
Comparison of different methods of determining cell viability after exposure to cytotoxic compounds.
It was found that the stainability of cells after drug exposure depended on the cell line used and the particular drug used, and cell survival as measured by cloning efficiency did not correlate with survival measured by any of the other methods.
An in vitro study of senescent events of human embryonic lung (WI-38) cells: I. Changes in enzyme activities of cellular and membrane associated enzymes of untreated and cortisone acetate-treated cultures during senescence
The decrease and/or increase in the other enzymes in the untreaetd and treated aged cultures strongly supports the point that there are alterations in total cellular metabolic functions in cells with age.
Quantitation of chemically induced neoplastic transformation of BALB-3T3 cloned cell lines.
Recloned, carcinogen-sensitive, BALB/3T3 cell lines present a reliable in vitro quantitative bioassay model for the study of chemical carcinogenesis.
Measurement of growth and rates of incorporation of radioactive precursors into macromolecules of cultured cells.
A method for measuring the incorporation of radioactive precursors into the RNA, DNA, and proteins of mammalian cells growing either as monolayers or in suspension is described, which eliminates time-consuming centrifugation.
A simultaneous coupling azo dye method for the histochemical demonstration of γ-glutamyl transpeptidase activity using the new substrate γ-glutamyl-4-methoxy-2-naphthylamide has been described. The