Cytogenetic effect of carboplatin on human lymphocytes.
Carboplatin, a second generation cisplatin analogue, was tested for induction of sister chromatid exchange (SCE) as well as chromosomal aberrations in human lymphocytes in vitro and in vivo. A dose-dependent effect was observed for increased frequency of metaphases with SCE (r = 0.984, P less than 0.001) as well as chromosomal aberrations (r = 0.994, P less than 0.001), primarily chromatid gap or break, in vitro. SCE induction by carboplatin was less than that by cisplatin at the same concentration. When patients were treated with a single dose of carboplatin at a dose of 450 mg/m2, the frequency of SCE and chromatid type aberrations increased significantly. However, even when considering dose and peak plasma concentration in patients receiving carboplatin, it appears that the ability of carboplatin to induce SCE and chromosomal aberrations is weaker than that of cisplatin. SCE frequencies induced by carboplatin decreased with time going by, and in one patient who was tested 5 weeks after treatment, SCE frequency showed a decrease to the pretreatment level. It thus appears that carboplatin has an improved therapeutic index over the parent compound, cisplatin, because of its less mutagenic or carcinogenic hazard, in addition to the largely reduced incidence of untoward effects.
Shinkai
T
T
Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan.
Saijo
N
N
Eguchi
K
K
Sasaki
Y
Y
Tamura
T
T
Sakurai
M
M
Suga
J
J
Nakano
H
H
Nakagawa
K
K
Hong
W S
WS
D000368:Aged; D016190:Carboplatin; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D009944:Organoplatinum Compounds; D016190:Carboplatin