Carboplatin AUC and gamma-glutamylcysteine synthetase gene expression in peripheral mononuclear cells of lung cancer patients.
BACKGROUND
To investigate the association between glutathione-related enzymes and carboplatin (CBDCA) dose, we examined gene expression levels for both subunits of gamma-glutamylcysteine synthetase (heavy; gamma-GCSh, light; gamma-GCS1) in peripheral mononuclear cells (PMN) of lung cancer patients before and after CBDCA administration.


METHODS
PMN and plasma samples were obtained from 10 advanced non-small lung cancer patients before and after CBDCA administration. We analyzed the gene expression levels by reverse transcription-polymerase chain reaction.


RESULTS
Gamma-GCSh expression levels in PMN increased within 24 hours after CBDCA administration, whereas gamma-GCS1 expression levels did not. However, the actual area under the concentration curve (AUC) of CBDCA did not correlate with gamma-GCSh expression at 24 hours or the increased ratio of gamma-GCSh expression in PMN.


CONCLUSIONS
Expression of gamma-GCSh is induced by CBDCA, however, CBDCA AUC is not a determinant for the increased expression levels of gamma-GCSh in PMN.
Oguri
T
T
Second Department of Internal Medicine, Hiroshima University School of Medicine, Japan. tetsuya@yahoo.co.jp
Isobe
T
T
Mitsuta
K
K
Masuda
K
K
Daga
H
H
Ishikawa
N
N
Fujitaka
K
K
Miyazaki
M
M
Kohno
N
N
D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D019540:Area Under Curve; D016190:Carboplatin / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D013921:Thrombocytopenia / Q000139:chemically induced
D000970:Antineoplastic Agents; D016190:Carboplatin; D005721:Glutamate-Cysteine Ligase