EMAIL THIS PAGE TO A FRIEND

Toxicological sciences : an official journal of the Society of Toxicology

Formation, Accumulation, and Hydrolysis of Endogenous and Exogenous Formaldehyde-Induced DNA Damage.


PMID 25904104

Abstract

Formaldehyde is not only a widely used chemical with well-known carcinogenicity but is also a normal metabolite of living cells. It thus poses unique challenges for understanding risks associated with exposure. N(2-)hydroxymethyl-dG (N(2)-HOMe-dG) is the main formaldehyde-induced DNA mono-adduct, which together with DNA-protein crosslinks (DPCs) and toxicity-induced cell proliferation, play important roles in a mutagenic mode of action for cancer. In this study, N(2)-HOMe-dG was shown to be an excellent biomarker for direct adduction of formaldehyde to DNA and the hydrolysis of DPCs. The use of inhaled [(13)CD2]-formaldehyde exposures of rats and primates coupled with ultrasensitive nano ultra performance liquid chromatography-tandem mass spectrometry permitted accurate determinations of endogenous and exogenous formaldehyde DNA damage. The results show that inhaled formaldehyde only reached rat and monkey noses, but not tissues distant to the site of initial contact. The amounts of exogenous adducts were remarkably lower than those of endogenous adducts in exposed nasal epithelium. Moreover, exogenous adducts accumulated in rat nasal epithelium over the 28-days exposure to reach steady-state concentrations, followed by elimination with a half-life (t1/2) of 7.1 days. Additionally, we examined artifact formation during DNA preparation to ensure the accuracy of nonlabeled N(2)-HOMe-dG measurements. These novel findings provide critical new data for understanding major issues identified by the National Research Council Review of the 2010 Environmental Protection Agency's Draft Integrated Risk Information System Formaldehyde Risk Assessment. They support a data-driven need for reflection on whether risks have been overestimated for inhaled formaldehyde, whereas underappreciating endogenous formaldehyde as the primary source of exposure that results in bone marrow toxicity and leukemia in susceptible humans and rodents deficient in DNA repair.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

A1542
Ammonium acetate, for molecular biology, ≥98%
C2H7NO2
A7330
Ammonium acetate, BioXtra, ≥98%
C2H7NO2
372331
Ammonium acetate, 99.999% trace metals basis
C2H7NO2
A7262
Ammonium acetate, reagent grade, ≥98%
C2H7NO2
A2706
Ammonium acetate solution, for molecular biology, 7.5 M
C2H7NO2
633178
Deuterium oxide, 99.994 atom % D, contains 1 mM terephthalic acid disodium salt, 0.01 % (w/v) DSS-d6
D2O
613398
Deuterium oxide, extra, 99.994 atom % D
D2O
191701
Deuterium oxide, "100%", 99.990 atom % D
D2O
364312
Deuterium oxide, standard, 99.98 atom %±0.01 atom % D
D2O
151890
Deuterium oxide, "100%", ≥99.96 atom % D
D2O
269786
Deuterium oxide, "100%", 99.96 atom % D
D2O
151882
Deuterium oxide, 99.9 atom % D
D2O
530867
Deuterium oxide, 99.9 atom % D
D2O
613444
Deuterium oxide, 99.9 atom % D, glass distilled
D2O
450510
Deuterium oxide, 99.9 atom % D, contains 0.05 wt. % 3-(trimethylsilyl)propionic-2,2,3,3-d4 acid, sodium salt
D2O
293040
Deuterium oxide, 99.9 atom % D, contains 0.75 wt. % 3-(trimethylsilyl)propionic-2,2,3,3-d4 acid, sodium salt
D2O
343773
Deuterium oxide, 99.9 atom % D, contains 1 % (w/w) 3-(trimethylsilyl)-1-propanesulfonic acid, sodium salt (DSS)
D2O
347167
Deuterium oxide, 99.9 atom % D, ~150 dpm/mL tritium
D2O
617385
Deuterium oxide, 99.8 atom % D
D2O
435767
Deuterium oxide, 99 atom % D
D2O
613436
Deuterium oxide, 60 atom % D
D2O
613428
Deuterium oxide, 70 atom % D
D2O
661643
Deuterium oxide, 99.99 atom % D (for D2O), contains 1% DSS-d6
D2O
756822
Deuterium oxide, filtered, 99.8 atom % D
D2O
L7875
DL-Leucine, ≥99% (HPLC)
C6H13NO2
158127
Paraformaldehyde, powder, 95%
CH2O ]n
441244
Paraformaldehyde, prilled, 95%
CH2O ]n
P6148
Paraformaldehyde, reagent grade, crystalline
CH2O ]n
RDD004
PIPES, anhydrous, free-flowing, Redi-Dri, ≥99%
C8H18N2O6S2
P6757
PIPES, ≥99% (titration)
C8H18N2O6S2