Assessment of in vivo chemotherapy-induced DNA damage in a p53-mutated rat tumor by micronuclei assay.
Production of DNA damage is the basis of cancer treatments such as chemo- and radiotherapy. Such treatments induce mitotic catastrophe, a form of cell death resulting from abnormal mitosis and leading to the formation of interphase cells with multiple micronuclei. In this study, we compared apoptosis induction and micronuclei formation to assess the DNA damage provoked in vivo by cytotoxic agents in established 9L rat gliosarcoma tumors expressing a mutated p53 gene. Results from TUNEL assays revealed the efficiency of local gamma-irradiation at the tumor site to induce apoptosis within 9L tumor mass. However, little or no apoptosis was detected after systemic (ip) injection of cisplatin (1 mg/kg). Interestingly, the micronuclei assays showed that not only gamma-irradiation but also cisplatin treatment led to an increase in the emergence of binucleated cells with micronuclei. Apoptosis induction and micronuclei emergence are thus not absolutely correlated. However, micronuclei assays, rarely performed on solid tumors, appear more sensitive than apoptosis assays in evaluating DNA damage linked to chemotherapy.
Driessens
Gregory
G
Interdisciplinary Research Institute (IRIBHM), School of Medicine, Université Libre de Bruxelles, 1070 Brussels, Belgium. gregory.driessens@ulb.ac.be
Harsan
Laura
L
Browaeys
Patrick
P
Giannakopoulos
Xenofon
X
Velu
Thierry
T
Bruyns
Catherine
C
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000627:therapeutic use*; D004249:DNA Damage / Q000187:drug effects; D016158:Genes, p53; D018316:Gliosarcoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D020287:In Situ Nick-End Labeling; D015162:Micronucleus Tests; D009154:Mutation; D051381:Rats
D000970:Antineoplastic Agents; D002945:Cisplatin