Almost a decade ago, based on analytical measurements of the oxidative DNA
adduct 8-oxo-deoxyguanosine (oxo(8)dG), it was reported that mitochondrial
DNA suffers greater endogenous oxidative damage than nuclear DNA. The subse
quent discovery that somatic deletions of mitochondrial DNA occur in humans
, and that they do so to the greatest extent in metabolically active tissue
s, strengthened the hypothesis that mitochondrial DNA is particularly susce
ptible to endogenous oxidative attack. This hypothesis was land is) appeali
ng for a number of reasons. Nevertheless, solid direct support for the hypo
thesis is lacking. Since the initial measurements, attempts to repeat the o
bservation of greater oxidation of mitochondrial DNA have resulted in a ran
ge of measurements that spans over four orders of magnitude. Moreover, this
range includes values that are as low as published values for nuclear DNA.
In the last 2 years or so, it has become apparent that the quantification
of oxidative DNA adducts is prone to artifactual oxidation. We have reporte
d that the analysis of small quantities of DNA may be particularly suscepti
ble to such interference. Because yields of mitochondrial DNA are generally
low, a systematic artifact associated with low quantities of DNA may have
elevated the apparent level of adduct oxo8dG in mitochondrial DNA relative
to nuclear DNA in some studies. Whatever the cause for the experimental var
iation, the huge disparity between published measurements of oxidative dama
ge makes it impossible to conclude that mitochondrial DNA suffers greater o
xidation than nuclear DNA. Despite the present confusion, however, there ar
e reasons to hypothesize that this is indeed the case. We briefly describe
methods being developed by a number of workers that are likely to surmount
current obstacles and allow the hypothesis to be tested definitively. (C) 1
999 Elsevier Science B.V. All rights reserved.