Abstract:
The allometric scaling relationship observed between metabolic rate (MR) and species
body mass can be partially explained by differences in cellular MR (Porter & Brand, 1995).
Here, I studied cultured cell lines derived from ten mammalian species to determine whether
cells propagated in an identical environment exhibited MR scaling. Oxidative and anaerobic
metabolic parameters did not scale significantly with donor body mass in cultured cells,
indicating the absence of an intrinsic MR setpoint. The rate of oxygen delivery has been
proposed to limit cellular metabolic rates in larger organisms (West et al., 2002). As such cells
were cultured under a variety of physiologically relevant oxygen tensions to investigate the
effect of oxygen on cellular metabolic rates. Exposure to higher medium oxygen tensions
resulted in increased metabolic rates in all cells. Higher MRs have the potential to produce more
reactive oxygen species (ROS) which could cause genomic instability and thus reduced lifespan.
Longer-lived species are more resistant to oxidative stress (Kapahi et al, 1999), which may be
due to greater antioxidant and/or DNA repair capacities. This hypothesis was addressed by
culturing primary dermal fibroblasts from eight mammalian species ranging in maximum
lifespan from 5 to 120 years. Only the antioxidant manganese superoxide dismutases (MnSOD)
positively scaled with species lifespan (p<0.01). Oxidative damage to DNA is primarily repaired
by the base excision repair (BER) pathway. BER enzyme activities showed either no correlation
or as in the case of polymerase p correlated, negatively with donor species (p<0.01 ). Typically,
mammalian cells are cultured in a 20% O2 (atmospheric) environment, which is several-fold
higher than cells experience in vivo. Therefore, the secondary aim of this study was to determine
the effect of culturing mammalian cells at a more physiological oxygen tension (3%) on BER,
and antioxidant, enzyme activities. Consistently, standard culture conditions induce higher
antioxidant and DNA ba.se excision repair activities than are present under a more physiological
oxygen concentration. Therefore, standard culture conditions are inappropriate for studies of
oxidative stress-induced activities and species differences in fibroblast DNA BER repair
capacities may represent differences in ability to respond to oxidative stress. An interesting
outcome firom this study was that some inherent cellular properties are maintained in culture (i.e.
stress responses) while others are not (i.e. MR).
