Changes in DNA Copy Numbers of Bovine Papillomavirus Type 1 After Termination of Retinoic Acid Treatment

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Abstract
The number of bovine papillomavirus type 1 (BPV) DNA copies [plasmid pdBPV-1 (142-6)] was examined in transformed C127 cells of an RIII mouse during exposure to all-trans-retinoic acid (RA) and after its withdrawal. RA treatment of a transformed cell line reduced the number from ≈60 copies to an average of less than one copy per cell within 5 weeks. The composition of the RA-treated cell population was heterogeneous with respect to BPV DNA copies: 89.7% of the cells had no detectable copies, 8.6% had one copy, 1.7% had fewer than five copies, and one in 13,000 cells carried more than 10 copies. The low number of BPV DNA copies in the RA-treated cell population did not increase when the cells were subcultured before reaching confluence. RA-treated cell populations that contained less than one BPV DNA copy lost the transformed phenotype. However, a small fraction of cells (1 in 13,000) with ≥10 BPV DNA copies retained the capacity to develop into transformed colonies. The relevance of these results to the regression of papillomavirus, DNA-Carrying human lesions after exposure to retinoids and the redevelopment of these lesions after withdrawal of retinoids is discussed. [J Natl Cancer Inst 1988;80:1567–1570]