Effect of cell confluence on ultraviolet light apoptotic responses in DNA repair deficient cells.
One of the major critical factors for cancer proneness is the cell response to DNA damage. In this work, we used human DNA repair deficient cell lines to investigate the responses to ultraviolet irradiation that lead to apoptosis, and the influence of maintaining the cells resting in confluent state. UV-induced apoptosis is prevented in photolyase-proficient HeLa cells when cyclobutane pyrimidine dimers (CPDs) are removed by photorepair. At the same time, we show recovery of RNA synthesis, thus indicating that blockage of RNA transcription may trigger apoptosis in human cells. On the other hand, confluent primary XPC and trichothiodystrophy (TTD)/XPD cell lines, related to xeroderma pigmentosum and trichothiodystrophy repair syndromes, had a reduced and delayed apoptosis when compared to non-confluent cells. In contrast, XPA cells were similarly sensitive in both the confluent and non-confluent growing state. The effect of cellular confluence on UV-mediated apoptosis in CSB cells, related to Cockayne's syndrome, was unclear. Thus, these results indicate that the induction of apoptosis by UV light may also be affected by DNA replication. In addition, they argue for the use of confluent primary cells in studies of induction of apoptosis by UV, a condition close to skin cells in vivo.
Carvalho
Helotonio
H
Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes, 1374, Ed. Biomédicas, 2, 05508-900 Sao Paulo, SP, Brazil.
da Costa
Renata Maria Augusto
RM
Chiganças
Vanessa
V
Weinlich
Ricardo
R
Brumatti
Gabriela
G
Amarante-Mendes
Gustavo P
GP
Sarasin
Alain
A
Menck
Carlos Frederico Martins
CF
D017209:Apoptosis / Q000528:radiation effects*; D002455:Cell Division / Q000528:radiation effects*; D002478:Cells, Cultured; D003057:Cockayne Syndrome / Q000235:genetics; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects*; D005347:Fibroblasts / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D014158:Transcription, Genetic / Q000187:drug effects; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics