UVB induces atypical melanocytic lesions and melanoma in human skin.
A direct causal relationship between ultraviolet (UV) light in the B range and melanoma development has not been demonstrated in humans; this study aims to establish causality. A total of 158 RAG-1 mice, grafted with human newborn foreskin, were separated into four groups and observed for a median of 10 months: 1) no treatment, 2) a single treatment with 7,12-dimethyl(a)benzanthracene (DMBA), 3) UVB irradiation at 500 J/m2 alone, three times weekly, and 4) a combination of DMBA and UVB. Twenty-three percent of 40 normal human skin grafts treated with UVB only and 38% of 48 grafts treated with the combination of DMBA and UVB developed solar lentigines within 5 to 10 months of treatment. Melanocytic hyperplasia was found in 73% of all UVB-treated xenografts. Histological melanocytic changes resembling lentigo and lentigo maligna were seen in several skin grafts treated with both DMBA and UVB. In one graft of an animal treated with a combination of DMBA and UVB, a human malignant melanoma, nodular type, developed. This experimental system demonstrates that chronic UVB irradiation with or without an initiating carcinogen can induce human melanocytic lesions, including melanoma.
Atillasoy
E S
ES
The Wistar Institute, the Department of Dermatology, Thomas Jefferson University, Philadelphia, Pennsylvania 19104, USA.
Seykora
J T
JT
Soballe
P W
PW
Elenitsas
R
R
Nesbit
M
M
Elder
D E
DE
Montone
K T
KT
Sauter
E
E
Herlyn
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D006965:Hyperplasia; D017403:In Situ Hybridization; D007231:Infant, Newborn; D008297:Male; D008544:Melanocytes / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D008545:Melanoma / Q000209:etiology / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000473:pathology*; D016511:Severe Combined Immunodeficiency / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology / Q000473:pathology*; D016038:Skin Transplantation; D014183:Transplantation, Heterologous; D014466:Ultraviolet Rays / Q000009:adverse effects*
D002273:Carcinogens; D004273:DNA, Neoplasm; D015127:9,10-Dimethyl-1,2-benzanthracene