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Roles of Cytomegalovirus and Chlamydia trachomatis in the Induction of Cervical Neoplasia in the Mouse¹

Departments of Pediatrics [A. D. H.], Pathology [A. D. H., J. W. R.], Reproductive Biology [W. B. W.], Medicine [D. D. A.], and Pharmacology [D. D. A.], Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio 44106

Cytomegalovirus and Chlamydia trachomatis are prevalent sexually transmissible pathogens. They produce persistent infections of the cervix and have been associated with cervical neoplasia. Cytomegalovirus has also been shown to induce transformation of cells in culture. Because of the high prevalence of genital infections with these pathogens and evidence that they may have oncogenic effects on the cervix, cytomegalovirus (strain AD-169) and C. trachomatis (serovar LGV-2) were tested for oncogenicity in a mouse model in which induction of cervical neoplasia by repeated exposure to inactivated herpes simplex viruses has been demonstrated previously. Cotton tampons, saturated with UV-inactivated cytomegalovirus, C. trachomatis, or corresponding control fluids, were inserted into the vaginas of virgin C57 mice 3 times a week. Smears of vaginal aspirates for cytological examination were obtained every 5 weeks. After 75–90 weeks of exposure, the mice were sacrificed and serial sections of their reproductive tracts were examined. Cervical dysplasia was detected by histological examination in 51% and cervical carcinoma in 10% of mice exposed to cytomegalovirus. In control mice, in contrast, dysplasia developed in 3% and carcinoma in none. The progression from normal cervical epithelium to dysplasia to carcinoma observed with cytomegalovirus exposure was similar to that observed previously in this model after exposure of mice to herpes simplex virus types 1 and 2. The frequencies of cervical abnormalities in mice exposed to C. trachomatis or corresponding control fluid were low, and differences between the two groups were not statistically significant. These data indicate that strain AD-169 of cytomegalovirus is oncogenic for the mouse cervix and suggest that the LGV-2 serovar of C. trachomatis is not.

¹ This investigation was supported by USPHS Grant CA-31973 awarded by the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed, at Department of Pediatrics, University Hospitals of Cleveland, 2074 Abington Road, Cleveland, OH 44106.

Received 10/25/85. Revised 3/26/86. Accepted 6/27/86.

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