Evidence for increased cytochrome P450 1A1 expression in blood lymphocytes of lung cancer patients.
To develop blood lymphocyte cytochrome P450 1A1 (CYP1A1) expression as a surrogate for monitoring tissue expression for polycyclic aromatic hydrocarbon (PAH) induced toxicity, the present study attempted to characterize CYP1A1 mRNA expression and its associated catalytic activity in freshly prepared blood lymphocytes isolated from healthy controls and patients suffering from tobacco induced lung cancer. Human blood lymphocytes were found to express CYP1A1 mRNA and significant activity of 7-ethoxyresorufin-O-deethylase (EROD). Significant increase in the activity of EROD and CYP1A1 mRNA was observed in blood lymphocytes isolated from patients suffering from lung cancer. Further, controls with variant genotypes of CYP1A1 (Msp1 or Ile/Val polymorphism) exhibited significant increase in the enzyme activity associated with an increase in CYP1A1 mRNA expression when compared to the controls with wild type genotype. Patients with variant genotypes of CYP1A1 also exhibited much greater increase in the blood lymphocyte CYP1A1 mRNA expression and EROD activity when compared to controls or patients with wild type genotype. Our data thus provides evidence of CYP1A1 expression in freshly isolated blood lymphocytes and differences in reactivity in individuals with variant genotypes of CYP1A1, suggesting that blood lymphocyte CYP1A1 expression profile could help in identifying individuals at risk to environment induced lung cancer.
Shah
Parag P
PP
Developmental Toxicology Division, Indian Institute of Toxicology Research (IITR), CSIR, MG Marg, Lucknow, UP, India.
Saurabh
Kumar
K
Pant
Mohan C
MC
Mathur
Neeraj
N
Parmar
Devendra
D
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008214:Lymphocytes / Q000201:enzymology*; D008297:Male; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects
D012333:RNA, Messenger; D019363:Cytochrome P-450 CYP1A1