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A monochromosomal hybrid cell assay for evaluating the genotoxicity of environmental chemicals

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The development and utilization of a monochromosomal hybrid cell assay for detecting aneuploidy and chromosomal aberrations are described. The monochromosomal hybrid cell lines were produced by a two-step process involving transfer of a marker bacterial gene to a human chromosome and then by integration of that human chromosome into a mouse complement of chromosomes through microcell fusion. For chemically induced aneuploidy, the segregation of a single human chromosome among mouse chromosomes is used as a cytogenetic marker. The genetic assay for aneuploidy is based on the ability of the cells to grow in a medium that selects for the loss of the human chromosome. The assay for clastogenicity is based on survival of the cells after treatment with the chemicals in medium that selects for retention of the human chromosome but loss of its segment containing diphtheria toxin locus. The assays greatly simplify the detection of chromosomal aberrations induced by environmental factors at low-dose levels.

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Abbreviations

CP:

cyclophosphamide

DT:

diphtheria toxin

Ecogpt:

E. coli gene for xanthineguanine phosphoribosyltransferase

hgprt:

hypoxanthine guanine phosphoribosyltransferase

MHC:

monochromosomal hybrid cell

MX:

mycophenolic acid and xanthine

PE:

plating efficiency

STT:

short-term test systems

6-TG:

6-thioguanine

XGPRT:

xanthine guanine phosphoribosyltransferase

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This manuscript has been reviewed by the Health Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

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Sandhu, S.S., Gudi, R.D. & Athwal, R.S. A monochromosomal hybrid cell assay for evaluating the genotoxicity of environmental chemicals. Cell Biol Toxicol 4, 495–506 (1988). https://doi.org/10.1007/BF00117777

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