title: Carboplatin AUC and gamma-glutamylcysteine synthetase gene expression in peripheral mononuclear cells of lung cancer patients.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Hiroshima University School of Medicine, Japan. tetsuya@yahoo.co.jp
authors.forename: T
authors.initials: T
authors.lastname: Oguri
authors.forename: T
authors.initials: T
authors.lastname: Isobe
authors.forename: K
authors.initials: K
authors.lastname: Mitsuta
authors.forename: K
authors.initials: K
authors.lastname: Masuda
authors.forename: H
authors.initials: H
authors.lastname: Daga
authors.forename: N
authors.initials: N
authors.lastname: Ishikawa
authors.forename: K
authors.initials: K
authors.lastname: Fujitaka
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
authors.forename: N
authors.initials: N
authors.lastname: Kohno
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D005721:Glutamate-Cysteine Ligase