Dose response and time course of carboplatin-induced micronucleated polychromatic erythrocytes in the cat: implications for combination carboplatin chemotherapy.
The dose response and time course of micronucleated polychromatic erythrocytes (mPCE) in cat peripheral blood induced by various doses (150-250 mg/m2) of carboplatin in vivo was determined. The data indicate that carboplatin produced a significant (p < 0.05) dose-dependent increase in the number of mPCE over baseline values; however, the times following carboplatin administration when mPCE were first observed differed significantly (p < 0.05) between the three carboplatin dose groups. mPCE were present in significantly greater numbers (p < 0.05) on smears at an earlier time interval following a single carboplatin dose of 150 mg/m2 than for a dose of either 200 or 250 mg/m2. The peak number of mPCE occurred on days 7, 14 and 17.5 following administration of a carboplatin dose of 150, 200 and 250 mg/m2, respectively. The pattern of time course delay following carboplatin administration suggests that the block of erythropoietic stem cells in G2 is dose dependent. Indeed, the administration of carboplatin arrested the cell cycle in the G2 phase and, at higher doses, diminished the number of cycling erythroid precursor cells. mPCE were apparent in blood smears only after recovery from this arrest and resumption of replication. This observation has implications for the scheduling of carboplatin administration when used in combination with other anticancer drugs.
Hahn
K A
KA
Department of Comparative Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071, USA. khahn@utk.edu
Fields
A
A
Hultgren
J L
JL
Nolan
M L
ML
Legendre
A M
AM
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000633:toxicity*; D002415:Cats; D002869:Chromosome Aberrations / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004913:Erythrocytes, Abnormal / Q000648:ultrastructure*; D005260:Female; D008297:Male; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D013997:Time Factors
D000970:Antineoplastic Agents; D009153:Mutagens; D016190:Carboplatin