Radiation-induced chromatid breaks and DNA repair in blood lymphocytes of patients with dysplastic nevi and/or cutaneous melanoma.
Each chromatid contains a single continuous molecule of double-stranded DNA, so chromatid breaks represent unrepaired DNA double-strand breaks. Frequencies of chromatid breaks after G2 phase x-irradiation were determined in phytohemagglutinin-stimulated blood lymphocytes from normal subjects and from four categories of patients with dysplastic nevi with or without cutaneous melanoma or with melanoma alone. Some cells were treated with an inhibitor of DNA repair replication to determine enzymatic incision activity at damaged sites after exposure to x-rays, UVC, or fluorescent light. Whereas one of 16 normal controls had deficient DNA repair, all 17 patients from families with hereditary dysplastic nevi with or without melanoma (category I) had a deficiency in repair of radiation-induced DNA damage, manifested as an abnormally high frequency of chromatid breaks after x-irradiation or a reduced capacity to incise the damaged sites after UV exposure. Four of 11 patients with sporadic dysplastic nevi alone (category II) and eight of 12 with sporadic dysplastic nevi and melanoma (category III) showed deficient DNA repair after x-irradiation. One of two patients with sporadic melanoma and no dysplastic nevi (category IV) was also deficient in repair of x-ray-induced damage. Deficient DNA repair thus appears to be associated with hereditary dysplastic nevi with or without melanoma. It also characterizes some patients with sporadic dysplastic nevi or melanoma.
Sanford
K K
KK
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892, U.S.A.
Parshad
R
R
Price
F M
FM
Tarone
R E
RE
Thompson
J
J
Guerry
D
D
D000293:Adolescent; D000328:Adult; D001773:Blood Cells / Q000502:physiology; D002842:Chromatids / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D004416:Dysplastic Nevus Syndrome / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D008545:Melanoma / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000097:blood / Q000235:genetics*