Oxidative damage to cellular biomolecules, in particular DNA, has been proposed to play an important role in a number of patholgical conditions, including carcinogenesis. A much studied consequence of oxygen-centred radical damage to DNA is 8-oxo-2′-deoxyguanosine (8-oxodG). Using numerous techniques, this lesion has been quantified in various biological matrices, most notably DNA and urine. Until recently, it was understood that urinary 8-oxodG derives solely from DNA repair, although the processes which may yield the modified deoxynucleoside have never been thoroughly discussed. This review suggests that nucleotide excision repair and the action of a specific endonuclease may, in addition to the nucleotide pool, contribute significantly to levels of 8-oxodG in the urine. On this basis, urinary 8-oxodG represents an important biomarker of generalised, cellular oxidative stress. Current data from antioxidant supplementation trials are examined and the potential for such compounds to modulate DNA repair is considered. It is stressed that further work is required to link DNA, serum and urinary levels of 8-oxodG such that the kinetics of formation and clearance may be elucidated, facilitating greater understanding of the role played by oxidative stress in disease.

Although exposure to exocannabinoids (e.g. marijuana) is associated with adverse pregnancy outcome, little is known about the biochemistry, physiology, and consequences of endocannabinoids in human pregnancy. In these studies, we measured the levels of the endocannabinoid anandamide (N-arachidonoylethanolamine, AEA) by HPLC-mass spectrometry in 77 pregnant and 25 nonpregnant women. The mean +/- sem plasma AEA levels in the first, second, and third trimesters were 0.89 +/- 0.14, 0.44 +/- 0.12, and 0.42 +/- 0.11 nm, respectively. The levels in the first trimester were significantly higher than those in either the second or third trimester. During labor, AEA levels were 3.7 times nonlaboring term levels (2.5 +/- 0.22 vs. 0.68 +/- 0.09 nm, P < 0.0001). During the menstrual cycle, levels in the follicular phase were significantly higher than those in the luteal phase (1.68 +/- 0.16 vs. 0.87 +/- 0.09 nm, P < 0.005). Postmenopausal and luteal-phase levels were similar to those in the first trimester. These findings suggest that successful pregnancy implantation and progression requires low levels of AEA. At term, AEA levels dramatically increase during labor and are affected by the duration of labor, suggesting a role for AEA in normal labor.

Of the DNA‐derived biomarkers of oxidative stress, urinary 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodG) is the most frequently measured. However, there is significant discrepancy between chromatographic and immunoassay approaches, and intratechnique agreement among all available chromatography‐based assays and ELISAs is yet to be established. This is a significant obstacle to their use in large molecular epidemiological studies. To evaluate the accuracy of intra/intertechnique and interlaboratory measurements, samples of phosphate buffered saline and urine, spiked with different concentrations of 8‐oxoG, together with a series of urine samples from healthy individuals were distributed to ESCULA members. All laboratories received identical samples, including 2 negative controls that contained no added 8‐oxodG. Data were returned from 17 laboratories, representing 20 methods, broadly classified as mass spectrometric (MS), electrochemical detection (EC), or enzyme‐linked immunosorbant assay (ELISA). Overall, there was good within‐technique agreement, with the majority of laboratories’ results lying within 1 SD of their consensus mean. However, ELISA showed more within‐technique variation than did the chromatographic techniques and, for the urine samples, reported higher values. Bland‐Altman plots revealed good agreement between MS and EC methods but concentration‐dependent deviation for ELISA. All methods ranked urine samples according to concentration similarly. Creatinine levels are routinely used as a correction factor for urine concentration, and therefore we also conducted an interlaboratory comparison of methods for urinary creatinine determination, in which the vast majority of values lay within 1 SD of the consensus value, irrespective of the analysis procedure. This study reveals greater consensus than previously expected, although concern remains over ELISA.—ESCULA [European Standards Committee on Urinary (DNA) Lesion Analysis], Evans, M. D., Olinski, R., Loft, S., Cooke, M. S. Toward consensus in the analysis of urinary 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine as a noninvasive biomarker of oxidative stress. FASEB J. 24, 1249–1260 (2010). www.fasebj.org