Dr. J. Justin McCormick

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Michigan State University
College of Osteopathic Medicine
University Distinguished ProfessorAppointed: 1992
Michigan State University
College of Osteopathic Medicine
Associate Dean for ResearchAppointed: 1987
Michigan State University
College of Osteopathic Medicine
Biochemistry and Molecular Biology
ProfessorAppointed: 1980
Michigan State University
College of Osteopathic Medicine
Microbiology and Molecular Genetics
ProfessorAppointed: 1980
Michigan State University
College of Osteopathic Medicine
Carcinogenesis Laboratory
Co-directorAppointed: 1976
Professional Headshot of J. Justin McCormick

Mailing Address

Carcinogenesis Laboratory
Michigan State University
Food Safety & Toxicology Bldg.
East Lansing, Michigan 48824-1302
United States

Contact Information

Phone: (517) 353-7785
Fax: (517) 353-9004
mccormi1@msu.edu
http://www.msu.edu/carcino

Qualifications

Ph.D., Catholic University of America, Cell Physiology, 1967.
M.S., Catholic University of America, Biology, 1963.
M.A., St. Paul's College, 1960.
B.S., St. Paul's College, 1957.

Expertise and Research Interests

My primary research interest is to define the genetic changes that are required to convert normal human cells to fully malignant (cancer) cells. For these studies we have utilized human fibroblasts as a model system. By sequential clonal selection, we have been able to produce a family of cell strains in which each of cell strains in the family have acquired a more transformed characteristic than the cell strains they were derived from. At each step, we have defined the gene change responsible for the increase in a transformed property. Recently, we noted that a transcription factor (i.e., a protein named Sp1) is much more highly expressed in 70% of the malignant cell strains we have derived. We postulated that this overexpression played a causal role in the ability of these cell strains to form cancers. To test this hypothesis, we designed a specific antisense strategy (Sp1 ribozyme) and used it to reduce the expression of Sp1 in the cancer cells. These cells lost the ability form tumors in athymic mice. Identical results were obtained when we used the same ribozyme to reduce the expression of Sp1 in cancer cells derived from fibroblastic cancers that occurred in human patients. We are currently testing whether the Sp1 ribozyme will inhibit the ability of cells derived from other types of human cancer that overexpress the Sp1 protein from forming tumors. We are also developing viruses carrying the Sp1 ribozyme to transduce this ribozyme into human tumors forming in athymic mice. We expect such treatment to block the growth of such tumors or reduce their rate of growth. If this is the case, such viruses can be used as a type of therapy against specific types of human cancers.

Keywords

COS Keywords:

Biochemistry, Cancer Genetics, Cancer Or Carcinogenesis, Chemical Carcinogenesis, Clinical Research or Studies, DNA Repair, Environmental Toxicology, Molecular Biology, Osteology or Osteopathy, Toxicology.

Additional Terms:

Cellular Mechanism of Carcinogenesis, Chemical Carcinogenesis, DNA Repair, Deoxyribonucleic Acid Repair, Environmental Toxicology, Human Cell Mutagenesis, Human Cell Transformation, Molecular Mechanism of Carcinogenesis, Radiation Carcinogenesis.

Languages

(Reading, Writing, Speaking)

English: (Fluent, Fluent, Fluent)
Latin: (Functional, Functional, Functional)

Memberships

American Association for Cancer Research
American Association for the Advancement of Science
American Society for Biochemistry
American Society for Photobiology
Environmental Mutagen Society
Radiation Research Society
Sigma Xi, The Scientific Research Society
Society for In-Vitro Biology

Honors and Awards

1990, Distinguished Faculty Award, Michigan State University

Previous Positions

1978-1980, Associate Professor, Michigan State University, College of Natural Science, Microbiology and Biochemistry
1976-1978, Associate Professor, Michigan State University, College of Osteopathic Medicine
1973-1976, Chief, Michigan Cancer Foundation, Molecular Biology Laboratory
1970-1973, Research Scientist, Michigan Cancer Foundation, Biology

Patents

Sp1 and Sp3 Targeted Cancer Therapies and Therapeutics, Patent Number: 60/486500, 2003, , United States of America.
J. Justin McCormick, Zhenjun Lou, Hongyan Liang, and Veronica M. Maher, Patent Number: , , , .

Funding Received

  • CA098305: Transformation of Infinite Life Span Human Fibroblasts, $890,000, May 1, 2003 to Apr 30, 2007.
  • CA82885: HGF/MET & Rho Family Proteins in Invasion & Metastasis, $459,533, Aug 1, 1999 to Jul 31, 2003.

Publications

  • Lou Z, Maher VM, McCormick JJ (May 2005) Identification of the promoter of human transcription factor Sp3 and evidence of the role of factors Sp1 and Sp3 in the expression of Sp3 protein., Gene, 351, 51-9 Abstract
  • Lou Z, O'Reilly S, Liang H, Maher VM, Sleight SD, McCormick JJ (Feb 2005) Down-regulation of overexpressed sp1 protein in human fibrosarcoma cell lines inhibits tumor formation., Cancer Research, 65 (3), 1007-17 Abstract
  • Liang H, O'Reilly S, Liu Y, Abounader R, Laterra J, Maher VM, McCormick JJ (May 2004) Sp1 regulates expression of MET, and ribozyme-induced down-regulation of MET in fibrosarcoma-derived human cells reduces or eliminates their tumorigenicity., International Journal of Oncology, 24 (5), 1057-67 Abstract
  • M. A. Battle, V. M. Maher, J. Justin McCormick, ST7 is a Novel Low-Density Lipoprotein Receptor-Related Protein (LRP) with a Cytoplasmic Tail that Interacts with Proteins Related to Signal Transduction Pathways, Biochemistry, 7270-7282, 2003
  • P. A. Havre, S. O'Reilly, J. J. McCormick, D.E. Brash., Transformed and tumor-derived human cells exhibit preferential sensitivity to the thiol antioxidants, N-acetyl cysteine and penicillamine, Cancer Research, 62, 1443-1449, 2002
  • Z. Li, W. Xiao, J. J. McCormick, V. M. Maher., Identification of a protein essential for a major pathway used by human cells to avoid UV-induced DNA damage Proc. Natl. Acad. Sci., USA, 99 (7), Natl. Acad. Sci., 4459-4464, 2002
  • Z. Li, H. Zhang, T. P. McManus, J. J. McCormick, C. W. Lawrence, V. M. Maher., Z. Li, H. Zhang, T. P. McManus, J. J. McCormick, C. W. Lawrence, V. M. Maher. hREV3 is essential for error-prone translesion synthesis past UV or benzo[a]pyrene diol-epoxide-induced DNA lesions in hum, Mutation Research, 510, 71-80, 2002
  • S.E. Boley, T.P. McManus, V.M. Maher, J.J. McCormick, Malignant transformation of human fibroblast cell strain MSU-1.1 by methylnitrosourea: evidence of homologous recombination to eliminate p53, Cancer Research, 60, 4105-4111, 2000
  • H. Zhang, G. Marra, B. Tung, J. Jiricny, V.M. Maher, J. J. McCormick., Postreplicative mismatch repair is required for O6-methylguanine-induced intrachromosomal homologous recombination in human fibroblasts, Carcinogenesis 20, 1639-1646, 2000
  • Huang S, Maher VM, McCormick J, Involvement of intermediary metabolites in the pathway of extracellular Ca2+-induced mitogen-activated protein kinase activation in human fibroblasts., Cell Signal, 11(4), 263-74, April 1999 Abstract
  • Qing J, Wei D, Maher VM, McCormick JJ, Cloning and characterization of a novel gene encoding a putative transmembrane protein with altered expression in some human transformed and tumor-derived cell lines., Oncogene, 18(2), 335-42, 14 Jan 1999 Abstract
  • McGregor WG, Wei D, Maher VM, McCormick JJ, Abnormal, error-prone bypass of photoproducts by xeroderma pigmentosum variant cell extracts results in extreme strand bias for the kinds of mutations induced by UV light., Molecular and Cellular Biology, 19(1), 147-54, Jan 1999 Abstract
  • Qing J, Maher V M, Tran H, Argraves W S, Dunstan R W, McCormick J J, Suppression of anchorage-independent growth and matrigel invasion and delayed tumor formation by elevated expression of fibulin-1D in human fibrosarcoma-derived cell lines., Oncogene, 15(18), 2159-68, October 1997 Abstract
  • McGregor W G, Wei D, Chen R H, Maher V M, McCormick J J, Relationship between adduct formation, rates of excision repair and the cytotoxic and mutagenic effects of structurally-related polycyclic aromatic carcinogens., Mutation Research, 376(1-2), 143-52, 12 May 1997 Abstract
  • Wei D, Maher V M, McCormick J J, Effect of nuclear environment on the distribution of benzo[a]pyrene diol epoxide-induced adducts in the HPRT gene of human fibroblasts., Carcinogenesis, 17(12), 2695-701, December 1996 Abstract
  • Zhang H, Tsujimura T, Bhattacharyya N P, Maher V M, McCormick J J, O6-methylguanine induces intrachromosomal homologous recombination in human cells., Carcinogenesis, 17(10), 2229-35, October 1996 Abstract
  • Wei D, Maher V M, McCormick J J, Site-specific excision repair of 1-nitrosopyrene-induced DNA adducts at the nucleotide level in the HPRT gene of human fibroblasts: effect of adduct conformation on the pattern of site-specific repair, Molecular and Cellular Biology, 16(7), 3714-9, July 1996 Abstract
  • Reinhold D S, Walicka M, Elkassaby M, Milam L D, Kohler S K, Dunstan R W, McCormick J J, Malignant transformation of human fibroblasts by ionizing radiation., International Journal of Radiation Biology, 69(6), 707-15, June 1996 Abstract
  • Tung B S, McGregor W G, Wang Y C, Maher V M, McCormick J J, Comparison of the rate of excision of major UV photoproducts in the strands of the human HPRT gene of normal and xeroderma pigmentosum variant cells., Mutation Research, 362(1), 65-74, 2 Jan 1996 Abstract
  • McGregor W G, Mah M C, Chen R W, Maher V M, McCormick J J, Lack of correlation between degree of interference with transcription and rate of strand specific repair in the HPRT gene of diploid human fibroblasts., Journal of Biological Chemistry, 270(45), 27222-7, 10 Nov 1995 Abstract
  • Carstens C P, Gallo J C, Maher V M, McCormick J J, Fahl W E, A system utilizing Epstein-Barr virus-based expression vectors for the functional cloning of human fibroblast growth regulators., Gene, 164(2), 195-202, 27 Oct 1995 Abstract
  • Lin C, Maher V M, McCormick J J, Malignant transformation of human fibroblast strain MSU-1.1 by v-fes requires an additional genetic change., International Journal of Cancer, 63(1), 140-7, 27 Sep 1995 Abstract
  • Huang S, Maher V M, McCormick J J, Extracellular Ca2+ stimulates the activation of mitogen-activated protein kinase and cell growth in human fibroblasts., Biochemical Journal, 310 ( Pt 3), 881-5, 15 Sep 1995 Abstract
  • Wei D, Maher V M, McCormick J J, Site-specific rates of excision repair of benzo[a]pyrene diol epoxide adducts in the hypoxanthine phosphoribosyltransferase gene of human fibroblasts: correlation with mutation spectra., Proceedings of the National Academy of Sciences (USA), 92(6), 2204-8, 14 Mar 1995 Abstract
  • Lin C, Wang Q, Maher V M, McCormick J J, Malignant transformation of a human fibroblast cell strain by transfection of a v-fes oncogene but not by transfection of a gag-human c-fes construct., Cell Growth and Differentiation, 5(12), 1381-7, December 1994 Abstract
  • Yang D, Kohler S K, Maher V M, McCormick J J, v-sis oncogene-induced transformation of human fibroblasts into cells capable of forming benign tumors., Carcinogenesis, 15(10), 2167-75, October 1994 Abstract
  • McGregor W G, Maher V M, McCormick J J, Kinds and locations of mutations induced in the hypoxanthine-guanine phosphoribosyltransferase gene of human T-lymphocytes by 1-nitrosopyrene, including those caused by V(D)J recombinase., Cancer Research, 54(15), 4207-13, 1 Aug 1994 Abstract
  • McCormick J J, Maher V M, Analysis of the multistep process of carcinogenesis using human fibroblasts., Risk Analysis, 14(3), 257-63, June 1994 Abstract
  • Ryan P A, Maher V M, McCormick J J, Failure of infinite life span human cells from different immortality complementation groups to yield finite life span hybrids., Journal of Cellular Physiology, 159(1), 151-60, April 1994 Abstract
  • Boyer J C, Thomas D C, Maher V M, McCormick J J, Kunkel T A, Fidelity of DNA replication by extracts of normal and malignantly transformed human cells., Cancer Research, 53(14), 3270-5, 15 Jul 1993 Abstract
  • Wang Y C, Maher V M, Mitchell D L, McCormick J J, Evidence from mutation spectra that the UV hypermutability of xeroderma pigmentosum variant cells reflects abnormal, error-prone replication on a template containing photoproducts., Molecular and Cellular Biology, 13(7), 4276-83, July 1993 Abstract
  • Maher V M, Bhattacharyya N P, Mah M C, Boldt J, Yang J L, McCormick J J, Mutations induced by 1-nitrosopyrene and related compounds during DNA replication in human cells and induction of homologous recombination by these compounds., Research Report / Health Effects Institute, 1-40; discussion 41-, March 1993 Abstract
  • Miller M J, Maher V M, McCormick J J, Quantitative two-dimensional gel electrophoresis analysis of human fibroblasts transformed by ras oncogenes., Electrophoresis, 13(11), 862-70, November 1992 Abstract
  • Wang Q, Maher V M, McCormick J J, Mammalian expression vectors with modulatable promoters and two multiple cloning sites., Gene, 119(2), 155-61, 1 Oct 1992 Abstract
  • Chen R H, Maher V M, Brouwer J, van de Putte P, McCormick J J, Preferential repair and strand-specific repair of benzo[a]pyrene diol epoxide adducts in the HPRT gene of diploid human fibroblasts., Proceedings of the National Academy of Sciences (USA), 89(12), 5413-7, 15 Jun 1992 Abstract
  • Yang D, Louden C, Reinhold D S, Kohler S K, Maher V M, McCormick J J, Malignant transformation of human fibroblast cell strain MSU-1.1 by (+-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene., Proceedings of the National Academy of Sciences (USA), 89(6), 2237-41, 15 Mar 1992 Abstract
  • Mah M C, Boldt J, Culp S J, Maher V M, McCormick J J, Replication of acetylaminofluorene-adducted plasmids in human cells: spectrum of base substitutions and evidence of excision repair., Proceedings of the National Academy of Sciences (USA), 88(22), 10193-7, 15 Nov 1991 Abstract
  • Morgan T L, Yang D J, Fry D G, Hurlin P J, Kohler S K, Maher V M, McCormick J J, Characteristics of an infinite life span diploid human fibroblast cell strain and a near-diploid strain arising from a clone of cells expressing a transfected v-myc oncogene., Experimental Cell Research, 197(1), 125-36, November 1991 Abstract
  • McGregor W G, Maher V M, McCormick J J, Kinds and locations of mutations arising spontaneously in the coding region of the HPRT gene of finite-life-span diploid human fibroblasts., Somatic Cell and Molecular Genetics, 17(5), 463-9, September 1991 Abstract
  • Lukash L L, Boldt J, Pegg A E, Dolan M E, Maher V M, McCormick J J, Effect of O6-alkylguanine-DNA alkyltransferase on the frequency and spectrum of mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine in the HPRT gene of diploid human fibroblasts., Mutation Research, 250(1-2), 397-409, September 1991 Abstract
  • Wang Y C, Maher V M, McCormick J J, Xeroderma pigmentosum variant cells are less likely than normal cells to incorporate dAMP opposite photoproducts during replication of UV-irradiated plasmids., Proceedings of the National Academy of Sciences (USA), 88(17), 7810-4, 1 Sep 1991 Abstract
  • Chen R H, Maher V M, McCormick J J, Lack of a cell cycle-dependent strand bias for mutations induced in the HPRT gene by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene in excision repair-deficien, Cancer Research, 51(10), 2587-92, 15 May 1991 Abstract
  • McGregor W G, Chen R H, Lukash L, Maher V M, McCormick J J, Cell cycle-dependent strand bias for UV-induced mutations in the transcribed strand of excision repair-proficient human fibroblasts but not in repair-deficient cells., Molecular and Cellular Biology, 11(4), 1927-34, April 1991 Abstract
  • Jankun J, Maher V M, McCormick J J, Malignant transformation of human fibroblasts correlates with increased activity of receptor-bound plasminogen activator., Cancer Research, 51(4), 1221-6, 15 Feb 1991 Abstract
  • Maher V M, Yang J L, Chen R H, McGregor W G, Lukash L, Scheid J M, Reinhold D S, McCormick J J, Use of PCR amplification of cDNA to study mechanisms of human cell mutagenesis and malignant transformation., Environmental and Molecular Mutagenesis, 18(4), 239-44, 1991 Abstract
  • Maher V M, Yang J L, Mah C M, Wang Y C, Boldt J, McCormick J J, Comparing the frequency and spectra of mutations induced when an SV40-based shuttle vector containing covalently bound residues of structurally-related carcinogens replicates in human cells., Advances In Experimental Medicine and Biology, 283, 183-91, 1991 Abstract
  • Yang J L, Chen R H, Maher V M, McCormick J J, Kinds and location of mutations induced by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in the coding region of the hypoxanthine (guanine) phosphoribosyltran, Carcinogenesis, 12(1), 71-5, January 1991 Abstract
  • Boldt J, Mah M C, Wang Y C, Smith B A, Beland F A, Maher V M, McCormick J J, Kinds of mutations found when a shuttle vector containing adducts of 1,6-dinitropyrene replicates in human cells., Carcinogenesis, 12(1), 119-26, January 1991 Abstract
  • Chen R H, Maher V M, McCormick J J, Effect of excision repair by diploid human fibroblasts on the kinds and locations of mutations induced by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene in th, Proceedings of the National Academy of Sciences (USA), 87(21), 8680-4, November 1990 Abstract
  • Maher V M, Domoradzki J, Bhattacharyya N P, Tsujimura T, Corner R C, McCormick J J, Alkylation damage, DNA repair and mutagenesis in human cells., Mutation Research, 233(1-2), 235-45, November 1990 Abstract
  • Norimura T, Maher V M, McCormick J J, Cytotoxic and mutagenic effect of UV, ethylnitrosourea and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene in diploid human T lymphocytes in culture: compariso, Mutagenesis, 5(5), 447-51, September 1990 Abstract
  • Fry D G, Milam L D, Dillberger J E, Maher V M, McCormick J J, Malignant transformation of an infinite life span human fibroblast cell strain by transfection with v-Ki-ras., Oncogene, 5(9), 1415-8, September 1990 Abstract
  • Wilson D M, Yang D J, Dillberger J E, Dietrich S E, Maher V M, McCormick J J, Malignant transformation of human fibroblasts by a transfected N-ras oncogene., Cancer Research, 50(17), 5587-93, 1 Sep 1990 Abstract
  • Bhattacharyya N P, Maher V M, McCormick J J, Effect of nucleotide excision repair in human cells on intrachromosomal homologous recombination induced by UV and 1-nitrosopyrene., Molecular and Cellular Biology, 10(8), 3945-51, August 1990 Abstract
  • Fox T R, Schumann A M, Watanabe P G, Yano B L, Maher V M, McCormick J J, Mutational analysis of the H-ras oncogene in spontaneous C57BL/6 x C3H/He mouse liver tumors and tumors induced with genotoxic and nongenotoxic hepatocarcinogens., Cancer Research, 50(13), 4014-9, 1 Jul 1990 Abstract
  • Norimura T, Maher V M, McCormick J J, A quantitative assay for measuring the induction of mutations in human peripheral blood T-lymphocytes., Mutation Research, 230(1), 101-9, May 1990 Abstract
  • Jiang L W, Maher V M, McCormick J J, Schindler M, Alkalinization of the lysosomes is correlated with ras transformation of murine and human fibroblasts., Journal of Biological Chemistry, 265(9), 4775-7, 25 Mar 1990 Abstract
  • Tsujimura T, Maher V M, Godwin A R, Liskay R M, McCormick J J, Frequency of intrachromosomal homologous recombination induced by UV radiation in normally repairing and excision repair-deficient human cells., Proceedings of the National Academy of Sciences (USA), 87(4), 1566-70, February 1990 Abstract
  • Bhattacharyya N P, Maher V M, McCormick J J, Intrachromosomal homologous recombination in human cells which differ in nucleotide excision-repair capacity., Mutation Research, 234(1), 31-41, February 1990 Abstract
  • Maher V M, Yang J L, McCormick J J, Amplification of mRNA of the hprt gene from lysates of mutant human cells and direct DNA sequencing to determine the spectrum of mutations induced by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha, e, Progress In Clinical and Biological Research, 340A, 379-88, 1990 Abstract
  • McCormick J J, Fry D G, Hurlin P J, Morgan T L, Wilson D M, Maher V M, Malignant transformation of human fibroblasts by oncogene transfection or carcinogen treatment., Progress In Clinical and Biological Research, 340D, 195-205, 1990 Abstract
  • Maher V M, Yang J L, McCormick J J, Ability of adducts formed in a shuttle vector by reactive metabolites of 1-nitropyrene and benzo(a)pyrene to induce mutations when the plasmid replicates in human cells., Acta Biologica Hungarica, 41(1-3), 173-86, 1990 Abstract
  • Mah M C, Maher V M, Thomas H, Reid T M, King C M, McCormick J J, Mutations induced by aminofluorene-DNA adducts during replication in human cells., Carcinogenesis, 10(12), 2321-8, December 1989 Abstract
  • Palmer H J, Maher V M, McCormick J J, Effect of retinoids on growth factor-induced anchorage independent growth of human fibroblasts., In Vitro Cellular and Developmental Biology, 25(11), 1009-15, November 1989 Abstract
  • Maher V M, Yang J L, Mah M C, McCormick J J, Comparing the frequency and spectra of mutations induced when an SV-40 based shuttle vector containing covalently bound residues of structurally-related carcinogens replicates in human cells., Mutation Research, 220(2-3), 83-92, March 1989 Abstract
  • Hurlin P J, Maher V M, McCormick J J, Malignant transformation of human fibroblasts caused by expression of a transfected T24 HRAS oncogene., Proceedings of the National Academy of Sciences (USA), 86(1), 187-91, January 1989 Abstract
  • Ryan, P.A., Maher, V.M., and McCormick, J.J. Failure of infinite life span cells from different immortality complementation groups to yield finite life span hybrids. J. Cell. Physiol. 159:151-160 (1994)
  • Yang, D., Kohler, S., Maher, V.M., and McCormick, J.J. V-sis oncogene-induced transformation of human fibroblasts into cells capable of forming benign tumors. Carcinogenesis 15:2167-2175 (1994)
  • Lin, C.-C., Wang, Q., Maher, V.M., and McCormick, J.J. Malignant transformation of a human fibroblast cell strain by transfection of a v-fes oncogene, but not a gag-human c-fes construct. Cell Growth and Differentiation 5:1381-1387 (1994)
  • Yang, D., Louden, C., Reinhold, D.S., Kohler, S.K., Maher, V.M., and McCormick, J.J. Malignant transformation of human fibroblast cell strain MSU-1.1 by (+)-7besta, 8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. Proc. Natl. Acad. Sci. (U.S.A.) 89:2237-2241 (1992)
  • Morgan, T.L., Yang, D., Fry, D.G., Hurlin, P.J., Kohler, S.K., Maher, V.M., and McCormick, J.J. Characteristics of an infinite life span diploid human fibroblasts cell strain and a near-diploid strain arising from a clone of cells expressing a transfected v-myc oncogene. Exp. Cell Res. 197:125-146 (1991)

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