Prolonged treatment with 5 muM all-trans retinoic acid (RA) resulted in the disappearance of viral DNA and phenotypic reversion in bovine papillomavirus (BPV) DNA-transformed mouse C127 cells (Int J Oncol 3: 319-324, 1993). The RA-induced revertants exhibited increased resistance to BPV DNA-induced cell transformation. Using selective hybridization techniques, we have cloned a cDNA sequence from an RA-induced revertant cell line, BF3RA10. Sequencing data reveals that the cDNA sequence was derived from the mitochondrial ND5 gene. When the cells were at low densities the amount of ND5 gene transcripts in the BPV DNA-transformed cells, the revertant cells and the parental C127 cells were similar. In confluent cultures, the abundance of ND5 gene transcripts did not change significantly in the revertant BF3RA10 cells, but decreased by several fold in the C127 and BPV DNA-transformed cells. In addition, the ND5 gene transcripts in the confluent C127 and BPV DNA transformed cells were mostly degraded. RA, a potent inhibitor of BPV DNA-mediated cell transformation, induced an increase in the abundance of ND5 mRNA. The comparative cell density-independent expression of ND5 gene in the transformation-resistant revertant cells and the RA-inducibility of ND5 gene suggest that mitochondrial gene expression is involved in the regulation of BPV DNA-mediated cell transformation.

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