The frequency of micronuclei in lymphocytes of dogs with osteosarcoma: a predictive variable for tumor response during cisplatin chemotherapy.
To our knowledge, there are no features identifiable at the time of diagnosis or during treatment that can assist the clinician in predicting the response to cisplatin therapy in dogs with osteosarcoma. In this study, we describe a direct relationship between the percentage of G0 lymphocytes containing micronuclei following exposure to one dose of cisplatin in vivo and tumor response in dogs with osteosarcoma. The response of tumors to chemotherapy is thought to be a function of the drug's pharmacological properties (e.g., peak plasma concentration and elimination half-life); however, a relationship between platinum DNA adduct levels in leukocyte DNA and tumor response has been observed by others, suggesting that clinical resistance to platinum drugs is attributable to DNA repair functions of the host, and thus the degree of cytotoxicity is similar across all cell types. Our results support this hypothesis. Those dogs receiving cisplatin chemotherapy and having a micronuclear frequency of greater than 10% had median remission and survival times of 68.3 and 79.0 weeks, respectively, whereas those dogs with a micronuclear frequency of less than 10% had median remission and survival times of 14.1 and 17.9 weeks, respectively.
Hahn
K A
KA
Department of Comparative Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071, USA.
Legendre
A M
AM
Talbott
J R
JR
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D004285:Dogs; D008214:Lymphocytes / Q000648:ultrastructure*; D048629:Micronuclei, Chromosome-Defective; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology*; D011237:Predictive Value of Tests; D012074:Remission Induction; D016192:Resting Phase, Cell Cycle; D016019:Survival Analysis
D000970:Antineoplastic Agents; D015415:Biomarkers; D004273:DNA, Neoplasm; D002945:Cisplatin