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Absence of Induction of Enhanced Reactivation of Herpes Simplex Virus in Cells from Xeroderma Pigmentosum Patients without Skin Cancer¹

Laboratory for Molecular Carcinogenesis, Sylvius Laboratories, P. O. Box 9503, 2300 RA Leiden, The Netherlands

The time course of appearance of enhanced reactivation (ER) and enhanced mutagenesis (EM) of herpes simplex virus type 1 were studied in UV-irradiated stationary cultures of xeroderma pigmentosum (XP) fibroblasts. In some of the XP cells EM followed similar kinetics of appearance as ER. Maximal activities occurred when infection was delayed 1 or 2 days after cell treatment. However, in certain XP cells only induction of the EM response was observed, whereas ER was absent. Interestingly, the latter XP cells had been obtained from patients who had not yet developed skin cancer at the time they were described in the literature, whereas the former XP patients had already developed skin tumors. This suggests that the ER response may somehow be involved in the process of oncogenic transformation. Dose-response studies of ER in XP cells from tumor-bearing patients showed that ER is maximally induced with a UV dose of 40 Jm^-2 given to the virus. Normal levels of ER were observed in 14 different normal human skin fibroblasts, indicating that the ER^- phenotype does not occur in normal cells or at least more rarely than in XP cells.

¹ This work was supported by the J. A. Cohen Institute, Interuniversity Research Institute for Radiopathology and Radiation Protection and by European Communities Contracts (B16-0169 NL; B16-0185 NL).

² To whom requests for reprints should be addressed, at Department of Medical Biochemistry, University of Leiden, P. O. Box 9503, 2300 RA Leiden, The Netherlands.

Received 3/24/88. Revised 7/19/88. Accepted 7/28/88.

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