Three independent cell lines were established from primary cultures of LSH hamster embryo cells infected with bovine papillomavirus type 1 (BPV-1). Although these cell lines differed in their in vitro saturation densities, none was capable of colony formation in soft agar. Interestingly, two cell lines (BPV-HE1 and BPV-HE3) were tumorigenic in nude mice, syngeneic hamsters, and allogeneic hamsters, whereas BPV-HE2 was not. All three cell lines contained similar numbers of the BPV-1 genome (approximately 50 to 200 copies per cell). However, the nontumorigenic BPV-HE2 cell line contained very low levels of BPV-specific RNA and only small amounts of the BPV-1 E5 transforming protein. The efficiency and rate of tumor formation by BPV-HE1 and BPV-HE3 correlated directly with the apparent amount of viral E5 protein. This analysis suggests that (i) there is a threshold level of BPV protein synthesis required for tumorigenicity, (ii) there is a continuum of tumorigenic phenotypes which may depend upon the level of BPV protein expression, and (iii) BPV-transformed hamster cells can withstand allogeneic transplantation.
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