This study compares over 70 recognition sites for
restriction endonucleases on mtDNAs from various control versus malignant cells, derived from Syrian hamster, chick embryo, viper and human cells, exhibiting a wide spectrum of cellular transformation and
tumor histories. Agents for transformation in vitro and in vivo include
Rous sarcoma viruses, simian virus 40, polyoma virus and adenovirus. The results show a striking intraspecific sequence homogeneity of different mtDNAs regardless of tissue origin and oncogenic history.
mtDNA from human biopsy specimens of
tumor versus pathologically normal areas yielded indistinguishable restriction cleavage patterns reflecting either the "wild-type' form (with seven
restriction endonucleases) or, in one individual, a variant pattern detected with HpaI. The precise position of the HpaI variant site was determined on the physical map of human
mtDNA. Additional cleavage sites in the previously reported restriction map of Syrian hamster
mtDNA are also presented. It is concluded that (1)
mtDNA sequence in higher animal cells are highly conserved in malignant transformation; (2) no evidence for integration of viral sequences in
mtDNA is apparent; (3) variant patterns in
mtDNA are likely to be intraspecific polymorphisms that pre-exist neoplastic transformation. The possibility is discussed that altered regulatory interaction with the mitochondrial genome, rather than evident changes in
mtDNA primary structure, determine anomalous mitochondrial functions in malignant transformation.