Formaldehyde in human cancer cells: Detection by preconcentration-chemicalionization mass spectrometry

A rapid and highly sensitive method for the detection of formaldehyde utili zing selected ion flow tube-chemical ionization mass spectrometry is report ed. Formaldehyde in aqueous biological samples is preconcentrated by distil lation and directly analyzed using gas-phase thermal energy proton transfer from H3O+; this procedure can be performed in 30 min. The method detection limit for formaldehyde based on seven replicate measurements of reference water samples (2.5 mL) is 80 nM at the 99% confidence level. Detection is l inear up to 130 muM. This technique allows the first measurement of natural formaldehyde levels in human cancer cells in vitro. Elevated levels of for maldehyde relative to the reference water are observed for doxorubicin-sens itive cells (MCF-7 breast cancer, K562 leukemia, HeLa 83 cervical cancer) w ith estimated intracellular formaldehyde concentrations ranging fi om 1.5 t o 4.0 muM, whereas formaldehyde in doxorubicin-resistant MCF-7/Adr breast c ancer cells is essentially at reference level. This trend is inverted for p rostate cancer cells LNCaP (sensitive) and DU-145 (resistant), Correlation of natural formaldehyde level with doxorubicin cytotoxicity is a function o f the expression of enzymes that neutralize oxidative stress and the drug e fflux pump, P-170 glycoprotein.