Effect of retinoic acid on bovine papillomavirus (BPV) DNA-induced transformation and number of BPV DNA copies.

The effect of all-trans-retinoic acid (RA) was examined on (1) transformation induced in C127 cells by transfection with plasmid pdBPV-1 (142-6), which contains DNA of bovine papillomavirus (BPV), (2) the capacity of transformed BPV DNA-containing clones to form colonies with transformed properties (e.g., piling up into multilayered colonies), and (3) the number of BPV DNA copies in transformed cells. At nontoxic doses ranging from 10(-7) to 10(-5) M, RA reduced the frequency of transformed foci in a dose-dependent manner. The extent of inhibition depended on the length of RA treatment and on the time that elapsed between DNA transfection and RA treatment. RA exerted only a slight inhibitory effect during the first days after transfection. Complete inhibition was observed when the cells were continuously exposed after transfection to RA at doses ranging from 0.5 to 1 X 10(-5) M. The inhibitory effect of RA on transformation was reversible. Transformed foci started to form after withdrawal of RA treatment. In the presence of RA (5 X 10(-6) M), cells from transformed colonies were no longer able to form foci displaying transformed properties. The number of BPV DNA copies gradually decreased when the cells were grown over several generations in the presence of RA (5 X 10(-6) M). After approximately 30 cell generations, the cell cultures appeared to have less than one copy of BPV DNA.