54 BIOLOGICAL EFFECTS OF LOW LEVEL EXPOSURES
Table 3.1. Age- and UV-Induced Repair in Rats. Hepatocytes Kidney Cells
(Months) Ad Lib Restricted Ad Lib Restricted
5 5.7 a a a
13 4.9 5.7 a a
22 3.1 4.0 2.0 2.4
28 2.7 3.3 1.3 1.9
34 a 3.0 a 1.3
Source: Data from Weraarchakul et al.14
Note: F-344 male rats; restricted are fed 60% of ad lib diet. All values are ratios of dpm//*g
DNA or radiated/irradiated cells after 1 hr. All ratios are significantly different (p <
0.01). Hepatocyes irradiated with 877 J/m2, kidney cells with 100 J/m2.
aNot done.
others compare cells from newborns to adults (confounding aging with
development); and many studies fail to adequately control differences in
cell replication,3 although it was shown clearly over 15 years ago that this
was an critical variable.4 However, some studies are useful to discuss.
Rat retinal ganglion cells treated in culture, from different aged animals,
demonstrated little change with age in the capacity to repair damage.5 Lens
epithelial cells also showed little change with age.6 Various older studies
using lymphocytes have given contradictory results; however, wide variabil
ity is one of the most salient characteristics.710 Recent studies with better
controls have been more definitive. Human lymphocytes do not seem to
exhibit an overall decrease in repair capability after maturity.11 However, a
more detailed study has shown that a small subset of aging cells, in fact, lose
their capability for repair of X-ray damage.12 Skin fibroblasts do not seem
to have major age-related changes.13 The situation is quite different in
hepatocytes and kidney cells.14 In those cells, there appears to be a definite
age-related decline in UV repair with age (Table 3.1).
Another approach to the relationship of aging and DNA repair compares
repair across species with differing life spans. Starting with Hart and
Setlow,15 a number of other studies have shown a good correlation between
life span and UV repair capacity in skin fibroblasts.3
One complicating factor in these studies, which has not been addressed at
all, is the circadian rhythm of DNA repair. This is illustrated in Table 3.2, in
which significantly different levels of DNA repair (06-methylguanine
Table 3.2. Circadian Variation in Oe-Methylguanine Repair
Time Activity(^1) 0.19
12 0.34
20 0.32
Source: Lipman et al.19
Note: Skin cells from 30-month-old B6C3F1 mice. Activity is 0 6-methylguanine acceptor
protein activity in pmols/mg DNA. Time is hours after lights on.