147
Bioehirniea et Biophysiea Acta, 442 (1976) 147--153 © Elsevier Scientific Publishing Company, Amsterdam -- Printed in The Netherlands
BBA 98651
COLONY-FORMING ABILITY OF ULTRAVIOLET-IRRADIATED XERODERMA PIGMENTOSUM FIBROBLASTS FROM DIFFERENT DNA REPAIR COMPLEMENTATION GROUPS
KENNETH H. KRAEMER, ALAN D. ANDREWS, SUSANNA F. BARRETT and JAY H. ROBBINS Dermatology Branch, National Cancer Institute, National Institutes o f Health, Bethesda, Md. 20014 (U.S.A.) (Received January 13th, 1976)
Summary Patients with x e r o d e n n a pigrnentosum develop severe sunlight-induced damage, including malignant neoplasms, on sun-exposed skin. Some pa~ents also have neurological abnormalities. Xeroderma pigrnentosum cells are known to have impaired ability to repair ultraviolet light- or chemical mutagen-induced damage to their D N A , and cell-fusion studies have shown five complementation groups among the D N A excision repair-deficient strains. All xeroderma pigmentosum fibrob!ast strains we tested had lower colony-forming abilities after ultraviolet irradiation than normal strains. Furthermore, we have found that strains from different complementation groups can have different postultrvviolet colony-forming abilitiesand that strains from patients with neurological abnormalities are the most sensitive to ultraviolet light. These results suggest that extremely ineffective repair of damaged D N A in central nervous system neurons may be the cause of the neurological abnormalities. Introduction
Xeroderma pigmentosum (XP) is a rare, autosomal recessive disease in which patients develop severe sunlight.induced cutaneous damage including malignant cutaneous neoplasms. Some X P patients also have associated neurological abnormalities caused by the premature death of neurons in the central nervous system. Numerous studies,utilizingseveral different physico-chemical assays of D N A repair, including ultraviolet-induced thymidine incorporation (unscheduled D N A synthesis), have shown that fibroblastsfrom most X P patients have iraAbbrevlnUon:XP, z~od~'ma Pi~#ntoi~m.
148 p ~ired ability to perform excision repair of ultraviolet-induced damage to their DNA
[i].
Unscheduled DNA synthesis has been analyzed in nuclei of binuclear heterokaryons obtained by fusing fibroblasts from pairs of XP strains. These studies revealed that certain pairs of strains, when fused, had a greater rate of unscheduled DNA synthesis than either s~Tain's unfused mononuclear cells, indicating that such complementing strain pairs had different DNA repair defects [2,3]. These cell fusion studies have demonstrated that there are at le~t five complementation groups (designated A to E) among excision repairdeficient XP fibrobiast strains [4]. Each of these complementation groups is associated with a characteristic rate of unscheduled DNA synthesis [3,4]. Prior to the discovery of XP complementation groups, it had been reported that excision repair
Bioehirniea et Biophysiea Acta, 442 (1976) 147--153 © Elsevier Scientific Publishing Company, Amsterdam -- Printed in The Netherlands
BBA 98651
COLONY-FORMING ABILITY OF ULTRAVIOLET-IRRADIATED XERODERMA PIGMENTOSUM FIBROBLASTS FROM DIFFERENT DNA REPAIR COMPLEMENTATION GROUPS
KENNETH H. KRAEMER, ALAN D. ANDREWS, SUSANNA F. BARRETT and JAY H. ROBBINS Dermatology Branch, National Cancer Institute, National Institutes o f Health, Bethesda, Md. 20014 (U.S.A.) (Received January 13th, 1976)
Summary Patients with x e r o d e n n a pigrnentosum develop severe sunlight-induced damage, including malignant neoplasms, on sun-exposed skin. Some pa~ents also have neurological abnormalities. Xeroderma pigrnentosum cells are known to have impaired ability to repair ultraviolet light- or chemical mutagen-induced damage to their D N A , and cell-fusion studies have shown five complementation groups among the D N A excision repair-deficient strains. All xeroderma pigmentosum fibrob!ast strains we tested had lower colony-forming abilities after ultraviolet irradiation than normal strains. Furthermore, we have found that strains from different complementation groups can have different postultrvviolet colony-forming abilitiesand that strains from patients with neurological abnormalities are the most sensitive to ultraviolet light. These results suggest that extremely ineffective repair of damaged D N A in central nervous system neurons may be the cause of the neurological abnormalities. Introduction
Xeroderma pigmentosum (XP) is a rare, autosomal recessive disease in which patients develop severe sunlight.induced cutaneous damage including malignant cutaneous neoplasms. Some X P patients also have associated neurological abnormalities caused by the premature death of neurons in the central nervous system. Numerous studies,utilizingseveral different physico-chemical assays of D N A repair, including ultraviolet-induced thymidine incorporation (unscheduled D N A synthesis), have shown that fibroblastsfrom most X P patients have iraAbbrevlnUon:XP, z~od~'ma Pi~#ntoi~m.
148 p ~ired ability to perform excision repair of ultraviolet-induced damage to their DNA
[i].
Unscheduled DNA synthesis has been analyzed in nuclei of binuclear heterokaryons obtained by fusing fibroblasts from pairs of XP strains. These studies revealed that certain pairs of strains, when fused, had a greater rate of unscheduled DNA synthesis than either s~Tain's unfused mononuclear cells, indicating that such complementing strain pairs had different DNA repair defects [2,3]. These cell fusion studies have demonstrated that there are at le~t five complementation groups (designated A to E) among excision repairdeficient XP fibrobiast strains [4]. Each of these complementation groups is associated with a characteristic rate of unscheduled DNA synthesis [3,4]. Prior to the discovery of XP complementation groups, it had been reported that excision repair
