Home LiteratureArticle Details
PMID: 284417 Published · ppublish English Journal Article

Chemical carcinogens produce mutations to ouabain resistance in transformable C3H/10T1/2 Cl 8 mouse fibroblasts.

Landolph JR, Heidelberger C

Abstract

Chemical carcinogens induce mutations to ouabain resistance in the transformable mouse fibroblast cell line C3H/10T1/2 Cl 8. The mutant phenotype is stable and heritable in the absence of selective agent, and dose--response curves for mutant frequency were obtained with N-menthyl-N'-nitro-N-nitrosoguanidine, 3-methylcholanthrene, benzo[a]-pyrene, N-acetoxy-N-2-acetylaminofluorene, and the anti-7,8-diol-9,10-epoxide of benzo[a]pyrene. The ratio of the malignant transformation frequency to the mutation frequency was 12 for benzo[a]pyrene and 21 for N-acetoxy-N-2-acetylaminofluorene. The development of the mutational assay reported here allows the use of this permanent cell line for comparison of mutation and transfomration frequencies and as a screening system for xenobiotics that pose mutagenic or carcinogenic hazards to mammalian cells.

MeSH Terms
2-Acetylaminofluorene/pharmacology Animals Carcinogens/pharmacology Cell Transformation, Neoplastic/drug effects Cells, Cultured Dose-Response Relationship, Drug Drug Resistance Methylnitronitrosoguanidine/pharmacology Mice Mice, Inbred C3H Mutation/drug effects Ouabain/pharmacology Time Factors
Chemicals
Carcinogens Methylnitronitrosoguanidine Ouabain 2-Acetylaminofluorene
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Landolph J R
Heidelberger C
References (33)
33 references, click to expand
  1. Clonal growth of mammalian cells in vitro; growth characteristics of colonies from single HeLa cells with and without a feeder layer.
    J Exp Med. 1956 Feb 1;103(2):273-83 PMID: 13286432
  2. IN VITRO CELL TRANSFORMATION WITH CHEMICAL CARCINOGENS.
    Nature. 1963 Dec 21;200:1182-4 PMID: 14089903
  3. Induction of ouabain-resistant mutations in C3H 10T1/2 mouse cells by ultraviolet light.
    Proc Natl Acad Sci U S A. 1978 Jul;75(7):3363-6 PMID: 150601
  4. Relationship between somatic mutation and neoplastic transformation.
    Proc Natl Acad Sci U S A. 1978 Jul;75(7):3297-301 PMID: 150600
  5. Liver cell-mediated mutagenesis of mammalian cells by liver carcinogens.
    Proc Natl Acad Sci U S A. 1978 Jun;75(6):2864-7 PMID: 149308
  6. Human bronchus-mediated mutagenesis of mammalian cells by carcinogenic polynuclear aromatic hydrocarbons.
    Proc Natl Acad Sci U S A. 1978 Apr;75(4):2003-7 PMID: 148049
  7. Relationships between mutation and transformation frequencies in mammalian cells treated "in vitro" with chemical carcinogens.
    Mutat Res. 1977;47(1):53-74 PMID: 342929
  8. Evidence for the progressive nature of neoplastic transformation in vitro.
    Proc Natl Acad Sci U S A. 1978 Aug;75(8):3761-5 PMID: 278986
  9. Cell density dependence of focus formation in the C3H/10T1/2 transformation assay.
    Cancer Res. 1977 Jun;37(6):1644-8 PMID: 558052
  10. Neoplastic transformation induced by a direct perturbation of DNA.
    Nature. 1978 Jul 20;274(5668):229-32 PMID: 683303
  11. Temporal acquistion of enhanced fibrinolytic activity by syrian hamster embryo cells following treatment with benzo(a)pyrene.
    Cancer Res. 1977 Oct;37(10):3815-23 PMID: 908023
  12. Mutagenesis at the ouabain-resistance locus in human diploid fibroblasts.
    Mutat Res. 1977 Sep;44(3):401-11 PMID: 904650
  13. Liver homogenate-mediated mutagenesis in chinese hamster V79 cells by polycyclic aromatic hydrocarbons and aflatoxins.
    Mutat Res. 1977 Feb 1;46(1):27-44 PMID: 840239
  14. Mutagenesis and transformation of normal cells by chemical carcinogens.
    Nature. 1976 Nov 25;264(5584):360-1 PMID: 1034212
  15. Quantitative and qualitative studies of chemical transformation of cloned C3H mouse embryo cells sensitive to postconfluence inhibition of cell division.
    Cancer Res. 1973 Dec;33(12):3239-49 PMID: 4796800
  16. Quantitative studies of in vitro transformation by chemical carcinogens.
    J Natl Cancer Inst. 1969 May;42(5):867-74 PMID: 4182072
  17. Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection.
    Proc Natl Acad Sci U S A. 1973 Aug;70(8):2281-5 PMID: 4151811
  18. Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division.
    Cancer Res. 1973 Dec;33(12):3231-8 PMID: 4357355
  19. Chemical oncogenesis in culture.
    Adv Cancer Res. 1973;18:317-66 PMID: 4357922
  20. In vitro transformation of Syrian hamster embryo cells by diverse chemical carcinogens.
    Nature. 1972 Feb 4;235(5336):278-80 PMID: 4551179
  21. The induction of ouabain-resistant mutants by N-methyl-N'-nitro-N-nitrosoguanidine in Chinese hamster cells.
    Genet Res. 1974 Dec;24(3):311-4 PMID: 4461312
  22. Ouabain-resistant human lymphoblastoid lines altered in the (Na+ + K+)-dependent ATPase membrane transport system.
    J Cell Physiol. 1976 July;88(3):343-52 PMID: 131808
  23. A quantitative system for assay of malignant transformation by chemical carcinogens using a clone derived from BALB-3T3.
    Int J Cancer. 1973 Sep 15;12(2):463-73 PMID: 4792350
  24. Quantitation of chemically induced neoplastic transformation of BALB-3T3 cloned cell lines.
    Cancer Res. 1972 Dec;32(12):2686-95 PMID: 4674680
  25. Somatic cell mutation. Detection and quantification of x-ray-induced mutation in cultured, diploid human fibroblasts.
    Mutat Res. 1973 May;18(2):199-224 PMID: 4711931
  26. Quantitative studies on the malignant transformation of mouse prostate cells by carcinogenic hydrocarbons in vitro.
    Int J Cancer. 1969 Mar 15;4(2):166-78 PMID: 4899788
  27. Mutagenicity to mammalian cells of epoxides and other derivatives of polycyclic hydrocarbons.
    Proc Natl Acad Sci U S A. 1971 Dec;68(12):3195-9 PMID: 5289256
  28. Chemical carcinogenesis.
    Annu Rev Biochem. 1975;44:79-121 PMID: 1094923
  29. Mutagenic and cytotoxic activity of benzol[a]pyrene 4,5-, 7,8-, and 9,10-oxides and the six corresponding phenols.
    Proc Natl Acad Sci U S A. 1975 Aug;72(8):3176-80 PMID: 1103140
  30. Identification of mutagenic metabolites of benzo(a)pyrene in mammalian cells.
    Proc Natl Acad Sci U S A. 1976 Feb;73(2):607-11 PMID: 1061161
  31. Exceptional mutagenicity of a benzo(a)pyrene diol epoxide in cultured mammalian cells.
    Nature. 1976 May 6;261(5555):52-4 PMID: 1272374
  32. A comparison of the 8-azaguanine and ouabain-resistance systems for the selection of induced mutant Chinese hamster cells.
    Mutat Res. 1975 Dec;33(2-3):261-78 PMID: 1240591
  33. Mutations to azaguanine resistance induced in cultured diploid human fibroblasts by the carcinogen, N-acetoxy-2-acetylaminofluorene.
    Mutat Res. 1975 May;28(2):227-84 PMID: 1134509
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1979-02-00
Pages
930-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC383096
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]