TEMPORAL AND HISTOLOGIC RELATIONSHIPS OF PROLIFERATING CELL NUCLEAR ANTIGEN AND HUMAN PAPILLOMAVIRUS TYPE-11 IN THE MOUSE XENOGRAFT SYSTEM

Proliferating cell nuclear antigen (PCNA) is an accessory protein of D NA polymerase delta. This protein is associated with cell cycle progre ssion and can be detected in the replicating cells of normal tissues. Condylomata acuminata are benign epithelial tumors caused by infection with human papillomaviruses and are characterized by abnormal cell pr oliferation. The athymic mouse xenograft model of HPV 11 infection was used to test the hypothesis that PCNA is induced early in the course of HPV 11 infection and to study the temporal and histologic relations hips between detection of PCNA and HPV DNA. Human foreskin tissue was infected with HPV 11 and implanted under the renal capsules of 10 athy mic mice. Pairs of mice were sacrificed every week beginning four week s after implantation. HPV DNA was detected in sections of foreskin imp lants by in situ hybridization. PCNA was as or more abundant in implan ts removed at earlier time points than at later time points, whereas H PV DNA became increasingly more abundant with time. PCNA was detected only in basal cells in areas of histologically normal epithelium that were also negative for HPV DNA. in contrast, PCNA was present througho ut the epithelium in regions that were HPV DNA-positive. HPV DNA was d etected only in differentiated epithelial cells in implants removed at all five time points, but in HPV DNA-positive regions, PCNA was detec ted with equal intensity in differentiated and undifferentiated cells. The foci of PCNA-positive cells were well demarcated and were larger than, but included, the foci of HPV DNA-positive cells. PCNA may be in duced maximally in differentiated epithelium by HPV 11 prior to signif icant HPV DNA replication. (C) 1996 Wiley-Liss, Inc.