Properties of two epithelial cell lines derived from HPV-associated cervical and vulvar lesions.

Two epithelial cell lines were established from human papilloma virus (HPV) 18 or 16 associated tumours, characterised as poorly and well differentiated squamous cell carcinomas of the cervix uteri (EC) and the vulva (GC), respectively. The cell lines are described by their morphology, biological parameters, and immunological markers. Both cell lines have undergone approximately 35 passages in vitro. HPV16 and 18 DNA are maintained integrated into the host cell DNA. Expression of epithelial cell markers--cytokeratins K1, K10, K13, K14 and involucrin, proliferation-specific proteins, proliferating cell nuclear antigen (PCNA) and Ki67 as well as the epidermal growth factor (EGF) receptor were monitored by indirect immunofluorescence studies. The cytoplasmic and membrane-associated locations of EGF receptor molecules in EC and GC cells, respectively, suggest a differently regulated expression. Studies of the HPV18 oncogene transcription revealed marked differences of amplimers between HeLa and EC cells, such as an additional fragment, probably corresponding to a E6**--E7 splice product, and a radical shift in transcription pattern observed in various sections of the tumour tissue. Injected subcutaneously into nu/nu mice both cell lines were non-tumorigenic.

Are transforming and mutagenic activities of oncogenic papovaviruses correlated?

A number of results obtained recently have shown that SV40-induced mutation and transformation of mammalian cells cultivated in vitro are related in some respect. Experiments were undertaken in order to get further information on the mode of mutagenic action of papovaviruses and further evidence of correlations existing between the mutagenic and transforming viral activities. DNA from the oncogenic hamster papovavirus HaPV was found to be mutagenic for at least three different resistance markers. In the hamster cell lines which were used HaPV DNA produced a higher yield of mutants than SV40 DNA for both the azaguanine and the aminopterin resistance marker. Cellular clones carrying a SV40-induced mutation in a specific locus were found to harbour viral genetic material and to exhibit a genetic instability of other loci. Also, cell lines characterized by their SV40-transformed state did exhibit such genetic instability. These results and results of other authors are discussed with respect to the correlations between oncogenic virus-induced mutation and transformation.