study where rats were subjected to exhaustive
exercise, we (Sen et al. 1997a) observed consistent
effects of physical exercise on tissue protein oxi-
dation. Protein carbonyl levels in the red gastroc-
nemius muscle were roughly three time higher in
exercised rats. In the vastus lateralis muscle,
exercise increased the carbonyl content by 69%.
Exhaustive exercise also increased protein oxida-
tion in the liver, but the effect was much less pro-
nounced than that in the muscles (Sen et al.
1997a). In another study, 10–15 min of swim exer-
cise resulted in oxidation of rat erythrocyte
membrane protein. Following exercise, skeletal
muscle microsomes contained decreased sul-
phydryls and protein cross-linking was exten-
sive (Rajguru et al. 1994). We observed that in
skeletal muscle cells certain membrane K+trans-
port proteins are highly sensitive to oxidant
exposure (Sen et al. 1995).
In humans, the number of oxidative hits to the
DNA per cell per day has been estimated to be as
high as 10 000 (Ames et al. 1993). Oxidative
lesions of DNA accumulate with age. A 2-year-
old rat is estimated to have two million oxidative
DNA lesions per cell, which is about twice that in
a young rat. In mammals, oxidative DNA
damage appears to be roughly related to the
metabolic rate (Ames et al. 1993). Such a trend,
suggesting a relationship between metabolic rate
and oxidative DNA damage, makes it important
to study the effect of exercise on oxidative DNA
modifications. Information regarding exercise-
induced oxidative DNA damage is limited,
however. Ten hours after marathon running, the
ratio of urinary oxidized nucleosides per creati-
nine increased 1.3-fold above rest (Alessio &
Cutler 1990). Neutrophils represent 50–60% of
the total circulating leucocytes, and Smith et al.
(1990) have shown that a single bout of exercise
may remarkably increase ROS production by the
neutrophils. We were therefore interested to see
how different intensities of exercise may affect
leucocyte DNA in humans. Results obtained in
our study (Sen et al. 1994d) indicate the possibil-
ity that exercise-associated oxidative stress may
initiate DNA damage in leucocytes. Out of the 36
measurements carried out with nine subjects
296 nutrition and exercise
during four exercise tests, DNA damage was not
detected in 11 cases, however. In another study,
no significant increase in the urinary level of the
oxidized RNA adduct 8-hydroxyguanosine fol-
lowing 90 min of bicycle exercise by young
healthy men was observed (Viguie et al. 1993). In
a later study, the single-cell gel test or COMET
assay was employed to detect exercise-induced
DNA damage in human white blood cells with
increased sensitivity. Incremental exercise on a
treadmill performed by healthy non-smoking
men clearly caused DNA damage (Hartmann
et al. 1995). Strenuous exercise for approximately
10 h · day–1for 30 days also increased the rate of
oxidative DNA modification by 33% (95% confi-
dence limits, 3–67%; P< 0.02) in 20 men. It was
suggested that oxidative DNA damage may
increase the risk of the development of cancer
and premature ageing in humans performing
strenuous exercise on a regular basis (Poulsen
et al. 1996).
Another line of evidence that supports the
hypothesis that physical exercise may induce
oxidative stress is the lowering of tissue levels
of antioxidants during exercise. In view of the
above-mentioned increases in tissue oxidative
stress indices following exercise, such lowering
of tissue antioxidant levels in response to physi-
cal exercise is thought to be a result of increased
antioxidant consumption in oxidative stress
challenged tissues. Several studies have shown
that physical exercise decreases tissue levels of
vitamin E (Goldfarb & Sen 1994). It is thought
that exercise-induced mobilization of free fatty
acids from the adipose tissues is accompanied by
the loss of tocopherols from the tissue. As a
result, tocopherol levels increased in human
blood following intense cycling. This elevation of
tocopherol levels in the circulation is transient
and the level returns to normal in the early phase
of recovery (Pincemail et al. 1988). Treadmill
exercise-induced decrease in total antioxidant
capacity of blood has also been evident in male
claudication patients (Khaira et al. 1995).
It has been consistently reported from several
laboratories (Gohil et al. 1988; Sen et al. 1994d;
Tessier et al. 1995; Vina et al. 1995; Laaksonen et al.