Individual responses to chemotherapy-induced oxidative stress
- 10 September 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Breast Cancer Research and Treatment
- Vol. 125 (2), 583-589
- https://doi.org/10.1007/s10549-010-1158-7
Abstract
Differences in redox homeostatic control between cancer patients may underlie predisposition to drug resistance and toxicities. To evaluate interindividual differences in redox response among newly diagnosed breast cancer patients undergoing standard chemotherapy, urine samples were collected before (T0), and at 1 (T1) and 24 h (T24) after chemotherapy administration. Oxidative status was assessed by urinary levels of allantoin and four F2-isoprostanes, quantified by LC–MS/MS. In all subjects, biomarker levels increased at T1 and returned to baseline at T24. Analyzing individual responses, two patterns were revealed: 10 subjects showed uniform increases of biomarker levels at T1 (“increase” pattern) and 8 subjects showed mixed (increase/unchanged/decrease) responses for different biomarkers (“mixed” pattern). The increase-pattern group had lower pre-treatment (T0) levels of the biomarkers and showed a sharp increase at T1 (64–141%) with a subsequent decrease at T24. The mixed-pattern group had higher pre-treatment biomarker levels and showed no change in biomarkers either at T1 or at T24. These findings indicate that there may be at least two distinct redox phenotypes with different homeostatic mechanisms balancing oxidative stress in humans. Recognizing redox phenotypes in human populations may lead to more precise assessment of health risks and benefits associated with individual redox make-up, and may also help to identify cancer patients who are especially susceptible to drug resistance and/or drug toxicity.Keywords
This publication has 30 references indexed in Scilit:
- Urinary Biomarkers of Oxidative Status in a Clinical Model of Oxidative AssaultCancer Epidemiology, Biomarkers & Prevention, 2010
- NAD(P)H Oxidase and Multidrug Resistance Protein Genetic Polymorphisms Are Associated With Doxorubicin-Induced CardiotoxicityCell Metabolism, 2005
- Redox-sensitive signaling factors as a novel molecular targets for cancer therapyDrug Resistance Updates, 2005
- Urinary F2‐Isoprostanes Are Not Associated with Increased Risk of Type 2 DiabetesObesity Research, 2005
- Metabolic control through the PGC-1 family of transcription coactivatorsCell Metabolism, 2005
- AMP-activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolismCell Metabolism, 2005
- Mitochondrial H+ leak and ROS generation: An odd coupleFree Radical Biology & Medicine, 2004
- Phosphorylated p40PHOX as a Negative Regulator of NADPH OxidaseBiochemistry, 2004
- Cellular levels of thioredoxin associated with drug sensitivity to cisplatin, mitomycin C, doxorubicin, and etoposide.1995
- The role of glutathione in radiation and drug induced cytotoxicity.1987