Mass Spectrometric Measurement of Formaldehyde Generated in Breast Cancer Cells upon Treatment with Anthracycline Antitumor Drugs
- 5 May 2000
- journal article
- research article
- Published by American Chemical Society (ACS) in Chemical Research in Toxicology
- Vol. 13 (6), 509-516
- https://doi.org/10.1021/tx000008m
Abstract
Selected ion flow tube-chemical ionization mass spectrometry was used to measure formaldehyde levels in human breast cancer cells in comparison with levels in cells treated with the antitumor drugs doxorubicin (DOX) and daunorubicin (DAU) and the daunorubicin−formaldehyde conjugate Daunoform (DAUF). The measurement was performed on cell lysates and showed only background levels of formaldehyde in untreated cells and drug-treated resistant cells (MCF-7/Adr cells) but levels above background in DOX- and DAU-treated sensitive cells (MCF-7 cells). The level of formaldehyde above background was a function of drug concentration (0.5−50 μM), treatment time (3−24 h), cell density (0.3 × 106 to 7 × 106 cells/mL), and cell viability (0−100%). Higher levels of formaldehyde were observed in lysates of MCF-7 cells treated at higher drug levels, unless the treatment resulted in low cell viability. Elevated levels were directly related to cell density and were observed even with 0.5 μM drug. A lower limit for excess formaldehyde in MCF-7 cells treated with 0.5 μM DAU for 24 h is 0.3 mM. Control experiments showed that formaldehyde was not produced after cell lysis. Lysates of sensitive and resistant cells treated with 0.5 micromolar equiv of the formaldehyde conjugate (DAUF) for 3 h showed only background levels of formaldehyde. The results support a mechanism for drug cytotoxicity which involves drug induction of metabolic processes leading to formaldehyde production followed by drug utilization of formaldehyde to virtually cross-link DNA.Keywords
This publication has 18 references indexed in Scilit:
- The secondary alcohol metabolite of doxorubicin irreversibly inactivates aconitase/iron regulatory protein‐1 in cytosolic fractions from human myocardiumThe FASEB Journal, 1998
- On-line monitoring of volatile organic compounds at pptv levels by means of proton-transfer-reaction mass spectrometry (PTR-MS) medical applications, food control and environmental researchInternational Journal of Mass Spectrometry and Ion Processes, 1998
- Doxoform and Daunoform: Anthracycline−Formaldehyde Conjugates Toxic to Resistant Tumor CellsJournal of Medicinal Chemistry, 1997
- Redox Pathway Leading to the Alkylation of DNA by the Anthracycline, Antitumor Drugs Adriamycin and DaunomycinJournal of Medicinal Chemistry, 1997
- Application of ion chemistry and the SIFT technique to the quantitative analysis of trace gases in air and on breathInternational Reviews in Physical Chemistry, 1996
- Base Specific and Regioselective Chemical Cross-Linking of Daunorubicin to DNAJournal of the American Chemical Society, 1996
- Stability of adriamycin-induced DNA adducts and interstrand crosslinksNucleic Acids Research, 1995
- Comparison of Different Iron Chelators as Protective Agents Against Acute Doxorubicin-induced CardiotoxicityJournal of Molecular and Cellular Cardiology, 1994
- Advances in flow reactor techniques for the study of gas‐phase ion chemistryMass Spectrometry Reviews, 1988
- The tandem flowing afterglow-shift-driftInternational Journal of Mass Spectrometry and Ion Processes, 1987