Xeroderma Pigmentosum Cells Contain LowLevels ofPhotoreactivating

Fibroblasts frompatients withxeroderma pigmentosumcontainlow levelsof photoreactivating enzymeincomparison tonormalcells. Levelsvaryfrom 0 (line 1199) to50(line 1259) percentofnormal.The de- pressed enzymelevels arenotan artifact oflowgrowth rate,ageofcelldonor,cellculture conditions, assaycon- ditions, thepresenceofinhibitors, ormycoplasmacon- tamination. We showthathuman fibroblasts canmono- merizepyrimidine dimersinvivo. Xeroderma pigmentosum isararedisease inwhichaffected individuals develop pigmentation abnormalities andmalig- nantgrowth inregions ofskinexposed tosunlight (1). Cells frommostxeroderma patients aredeficient intheunsched- uledDNA synthesis elicited byultraviolet light (220-300 nm)innormal cells (2); these cells arethought tolackat least oneoftheenzymes involved inexcision repair ofultra- violet light (UV)-induced damagetoDNA (3). However, the existence ofxeroderma variants, individuals withapparently normal unscheduled DNA synthesis butwithalltheclinical manifestations ofxeroderma pigmentosum (4), andthelim- ited genetic analysis currently available duetotherareness of thedisease, suggested thatother factors mightcontribute to themolecular origin ofthis sun-induced skin cancer (1). Inphotoreactivation, UV-induced cyclobutyl pyrimidine dimers inDNA arerepaired bythephotoreactivating enzyme inatwo-step reaction: theenzyme binds toadimer-containing region ofDNA,andinthepresence oflight ofwavelengths be- tween300and600nmmonomerizes thedimer, thusrestoring biological activity totheDNA (5,6).Until recently, the photoreactivating enzymewasthought tobeabsent from placental mammals(7,8).However, since Sutherland (9)has recently demonstrated thepresence oftheenzymeinhuman leukocytes, andSutherland etal.(10) havefound theenzyme inmurine andhumanfibroblasts, wehaveexamined thelevel