Absence of DNA repair deficiency in the confirmed heterozygotes of xeroderma pigmentosum group A.

This study was performed to elucidate whether xeroderma pigmentosum complementation group A (XPA) carrier has DNA repair abnormality against sun-exposure and ultraviolet (UV)-mimetic chemical carcinogen 4-nitroquinoline 1-oxide (4NQO). Here we report three sporadic cases of XP that were defined as group A by genetic complementation test as well as polymerase chain reaction (PCR) analysis to detect the point mutation in the responsible gene for XPA. DNA repair analyses in the skin fibroblasts revealed that the cells from the patients were much more sensitive to UV and 4NQO and had extremely low UV-induced unscheduled DNA synthesis (UDS) than control cells, whereas the cells from the carriers (heterozygotes of XP) had sensitivity to UV and 4NQO and levels of UV-induced UDS similar to normal cells. These results indicate that the obligate heterozygotes, despite having a mutated allele in XPA complementing gene demonstrated by PCR, have no DNA repair abnormality after UV irradiation and UV-mimetic 4NQO treatment. Our observations imply that XPA heterozygotes do not have higher risk of skin cancers than normal subjects based on their DNA repair abnormality.