ATM heterozygote cells exhibit intermediate levels of apoptosis in response to streptonigrin and etoposide.
Ataxia-telangiectasia (A-T) is a rare recessive disease characterised by cerebellar ataxia, immunodeficiency, sensitivity to ionising radiation and increased cancer risk. Heterozygotes have an increased risk of cancer and may comprise 1% of the population. In vitro, A-T heterozygote cell lines show radiosensitivity intermediate between normal and A-T homozygotes. Furthermore, in A-T homozygotes, hypersensitivity to chemical agents which cause DNA damage, similar to that produced by ionising radiation, has been observed. To investigate the chemosensitivity of A-T heterozygote cell lines, we used TUNEL to analyse the level of apoptosis after drug treatment with etoposide and streptonigrin. Our samples included four normal, eight A-T heterozygote and 10 A-T homozygote lymphoblastoid cell lines. All cell lines were exposed to drugs for 24 h, then cultivated in fresh media for 0 and 72 h. The levels of apoptosis increased significantly in all cell lines, with the greatest increase in homozygote cells and an intermediate increase in heterozygote cells (P values of < 0.01 for etoposide treatment and < 0.02 for streptonigrin treatment were obtained using the Kruskal-Wallis H-test). Our results indicate that A-T heterozygotes express intermediate sensitivity to etoposide and streptonigrin similar to that observed in response to ionising radiation.
Pernin
D
D
Laboratoire d'Oncologie Moléculaire, CRI 9502 & EA 2145, Centre Jean Perrin, Clermont-Ferrand, France.
Bay
J O
JO
Uhrhammer
N
N
Bignon
Y J
YJ
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D001260:Ataxia Telangiectasia / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D002460:Cell Line; D005047:Etoposide / Q000627:therapeutic use*; D006580:Genetic Carrier Screening; D006579:Heterozygote; D006801:Humans; D013308:Streptonigrin / Q000627:therapeutic use*
D013308:Streptonigrin; D005047:Etoposide