An apoptosis-inducing genotoxin differentiates heterozygotic carriers for Werner helicase mutations from wild-type and homozygous mutants.
Immortalized B lymphocytes from Werner syndrome subjects are shown to be hypersensitive to 4-nitroquinoline-1-oxide (4NQO), supporting earlier work on T lymphocytes. We also show that B cell lines from clinically normal heterozygous carriers exhibit sensitivities to this genotoxic agent, which are intermediate to those of wild-type and homozygous mutants. 4NQO is shown to induce an apoptotic response. These data encourage research on DNA repair with such cell lines and raise the question of an enhanced sensitivity of the relatively prevalent heterozygous carriers to certain environmental genotoxic agents.
Ogburn
C E
CE
Oshima
J
J
Poot
M
M
Chen
R
R
Hunt
K E
KE
Gollahon
K A
KA
Rabinovitch
P S
PS
Martin
G M
GM
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics*; D001402:B-Lymphocytes / Q000187:drug effects; D002460:Cell Line; D004265:DNA Helicases / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005090:Exodeoxyribonucleases; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation; D010641:Phenotype; D053484:RecQ Helicases; D014898:Werner Syndrome / Q000201:enzymology / Q000235:genetics*; D000071657:Werner Syndrome Helicase
D009153:Mutagens; D015112:4-Nitroquinoline-1-oxide; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase