This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hayashi, J.-I. Articles by Tagashira, Y. Search for Related Content PubMed PubMed Citation Articles by Hayashi, J.-I. Articles by Tagashira, Y.

Nuclear but not Mitochondrial Genome Involvement in 3-Methylcholanthrene-induced Expression of Tumorigenicity in Mouse Somatic Cells¹

Department of Biochemistry, Saitama Cancer Center Research Institute, Ina, Saitama 362, Japan

The involvement of heritable modifications of mitochondrial DNA (mtDNA) in chemical carcinogenesis was examined by studies on the effects on tumorigenicity of interchange of mtDNA between 3-methyl-cholanthrene (MCA)-induced mouse tumor cells and nontumorigenic mouse cells by the cytoplast-to-cell fusion technique. The difference in propagating abilities of two types of mouse mtDNA, type 1 mtDNA of B10mtJ strain and type 2 mtDNA of C57BL/10 strain, was applied successfully for complete replacement of the host cell mtDNA by cytoplasmically transmitted mtDNA. Tumorigenicity was assayed in nude mice by inoculating 5 x 10⁶ cells s.c. into the backs of the mice. The results showed that tumorigenicity was not induced in nontumorigenic cells by replacement of their mtDNA by that from MCA-induced tumor cells. Moreover, the tumorigenicity of MCA-induced tumor cells was still expressed when their mtDNA was replaced by that from normal cells with a limited life span. These observations suggest that, even if MCA treatment causes heritable modifications of mtDNA, modified mtDNA cannot induce chemical carcinogenesis and that modifications of nuclear DNA alone are sufficient for the expression of tumorigenicity.

¹ This work was partly supported by grants from the Naito Foundation to J-I. H.; by Grants-in-Aid for Scientific Research on Priority Areas, No. 62617522 (Bioenergetics) to J-I. H. and No. 62619510 to J-I. H. and H. Y.; and by Grants-in-Aid for Cancer Research, No. 62010073 to H. Y., from the Ministry of Education, Science, and Culture, Japan.

² To whom requests for reprints should be addressed.

Received 10/24/88. Revised 4/13/89. Accepted 5/ 9/89.

This article has been cited by other articles:

				K. Inoue, S. Ito, D. Takai, A. Soejima, H. Shisa, J.-B. LePecq, E. Segal-Bendirdjian, Y. Kagawa, and J.-I. Hayashi Isolation of Mitochondrial DNA-less Mouse Cell Lines and Their Application for Trapping Mouse Synaptosomal Mitochondrial DNA with Deletion Mutations J. Biol. Chem., June 13, 1997; 272(24): 15510 - 15515. [Abstract] [Full Text] [PDF]

				R. Dey, A. Barrientos, and C. T. Moraes Functional Constraints of Nuclear-Mitochondrial DNA Interactions in Xenomitochondrial Rodent Cell Lines J. Biol. Chem., September 29, 2000; 275(40): 31520 - 31527. [Abstract] [Full Text] [PDF]