Human Teratoma Cell Culture System For The Presceening Of Environmental Chemicals That May Initiate Or Promote Tumor Formation.

Details

• Personal Author:
  Huberman E ; Jones CA
• Description:
  A human teratoma cell culture system that can be used to detect a variety of chemical mutagens was described. The system used an epithelial cell line, designated P3, which was cloned from a human teratoma cell line. The induction of mutations at the hypoxanthine- guanine-phosphoribosyl-transferase (HGPRT) locus, situated on the X- chromosome, rendered the cells resistant to the nucleic acid analogue 6-thioguanine (thioguanine). The loss of HGPRT enzyme activity could arise from a variety of genetic insults at this locus, including frameshift mutations, base pair substitutions, chromosomal aberrations, and deletions. The mutability of the P3 cells for thioguanine resistance was evaluated using benz(a)pyrene (50328) (BaP) and N-methyl-N'-nitro-N-nitrosoguanidine (70257) (MNNG). The cloning efficiency of the P3 cells was 69 percent, whereas the cloning efficiency of the mutant cells ranged from 45 to 75 percent. The effects of MNNG or BaP on HGPRT activity in P3 cells and clones were determined. HGPRT enzyme activity was reduced by more than 10 fold in the clones, compared to P3 cells. Thioguanine resistant P3 cells were activated with human BJ cells and incubated with benzo(e)pyrene (192972) (BeP), pyrene (129000), chrysene (218019), BaP, 3-methylcholanthrene (56495) (MCA), or 7,12- dimethylbenz(a)anthracene (57976) (DMBA) and assayed for the induction of thioguanine resistant mutants. DMBA, MCA, BaP, and chrysene induced thioguanine resistant mutants, the degree of induction being directly related to their carcinogenic potency. Pyrene and BeP were inactive or exhibited a limited induction of thioguanine resistant mutants. The authors conclude that the human P3 epithelial cell mutagenesis assay can detect genetic damage induced by physical agents and direct acting and proximate mutagens or carcinogens. [Description provided by NIOSH]
• Subjects:
  Biological Assay Carcinogens Chromosomes Enzymes Genetics Histocytochemistry Mutagens Occupational Health Safety
• Keywords:
  Cell-biology; Mutagenicity; Enzyme-activity; Genetic-factors; Carcinogenesis; Cytochemistry; Biological-function; Physiological-response; Chromosome-damage; Bioassays
• Document Type:
  Text
• Genre:
  Report
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  189-214
• NIOSHTIC Number:
  nn:00156956
• Citation:
  NIOSH 1984:189-214
• CAS Registry Number:
  3-Methylcholanthrene (CAS RN 56-49-5) ; 7,12-Dimethylbenz[a]anthracene (CAS RN 57-97-6) ; Benzo[a]pyrene (CAS RN 50-32-8) ; Benzo[e]pyrene (CAS RN 192-97-2) ; Chrysene (CAS RN 218-01-9) ; N-Methyl-N′-nitro-N-nitrosoguanidine (CAS RN 70-25-7) ; Pyrene (CAS RN 129-00-0)
• Federal Fiscal Year:
  1984
• Peer Reviewed:
  False
• Source Full Name:
  Proceedings of the Third NCI/EPA/NIOSH Collaborative Workshop: Progress on Joint Environmental and Occupational Cancer Studies
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7dc847c09aedf140bc731323e8446b4703641ae07d6ad9e7b7238120dab30b8f7dcaa9b938d34d035f87873a0fe7fec262d5d13dcaf290925445e82b6de3b57d
• Download URL:
  https://stacks.cdc.gov/view/cdc/242148/cdc_242148_DS1.pdf
• File Type:
  [PDF - 168.02 KB ]