Comparison of the responses of human melanocytes with different melanin contents to ultraviolet B irradiation.
Melanin is thought to serve in photoprotection. To investigate this, we have compared the responses of cultured human melanocytes derived from different pigmentary phenotypes (skin types I-VI) to a single irradiation with different doses of UVB light, ranging between 11.7 and 70.1 mJ/cm2. After UVB irradiation, heavily pigmented melanocytes had the same percent survival but a greater capacity to resume proliferation than their lightly pigmented counterparts. A significant increase in melanin content was observed in heavily pigmented but not in lightly pigmented melanocytes. Irradiation with UVB light blocked melanocytes, regardless of their melanin content, in G1, and induced the expression of the tumor suppressor p53 protein within 4 h. This induction steadily increased up to 48 h in lightly pigmented melanocytes; however, in heavily pigmented melanocytes, p53 level peaked at 24 h after UVB treatment and declined thereafter. Additionally, DNA from lightly pigmented melanocytes contained significantly higher numbers of cyclobutane pyrimidine dimers than did DNA from heavily pigmented melanocytes after irradiation with increasing doses of UVB light. We speculate that the prolonged induction of p53 in lightly pigmented melanocytes arrests them in G1 for a long time period in order to repair extensive DNA damage. The above described differences might partially explain the increased susceptibility of individuals with lightly pigmented skin compared to individuals with dark skin to the photodamaging and photocarcinogenic effects of sun exposure.
Barker
D
D
Department of Dermatology, University of Cincinnati, Ohio 45267-0592, USA.
Dixon
K
K
Medrano
E E
EE
Smalara
D
D
Im
S
S
Mitchell
D
D
Babcock
G
G
Abdel-Malek
Z A
ZA
D002453:Cell Cycle / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D016158:Genes, p53; D006801:Humans; D008543:Melanins / Q000032:analysis* / Q000502:physiology; D008544:Melanocytes / Q000737:chemistry / Q000528:radiation effects*; D011740:Pyrimidine Dimers / Q000378:metabolism; D014466:Ultraviolet Rays
D008543:Melanins; D011740:Pyrimidine Dimers