Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 50, Issue 5 B303-B306, Copyright © 1995 by The Gerontological Society of America
Alterations in activation and deactivation of mutagens in aging rat liver
M Masuda, C Nukuzuma, A Kazusaka and S Fujita
Department of Toxicology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Age-associated alternations in activation and deactivation of
benzo[a]pyrene (BP), furylfuramide (AF2), and 2-nitrofluorene (NF) in rat
liver were investigated. A modified Ames mutagenicity test system used
liver 9000 g supernatant (S-9) from male Fischer 344 rats aged 3, 6, 12,
and 24 months fortified with NADPH generating system alone or together with
cofactors of conjugating enzymes. The numbers of revertant colonies due to
mutagenic activation of BP during preincubation were markedly high in young
rats and decreased with aging. They were decreased by the addition of
UDP-glucuronic acid (15 mM) or glutathione (30 mM), the cofactors of
UDP-glucuronyl transferase and glutathione S-transferase, respectively, in
the preincubation mixture. The difference in the BP activation by liver S-9
from different age groups almost disappeared by the addition of reduced
glutathione. A direct mutagen, AF2, was not metabolized during
preincubation in the absence of cofactors of conjugating enzymes, but
detoxified up to about 50% by the addition of glutathione to the
preincubation mixture containing liver S-9 from rats of any age group.
Another direct mutagen, NF, was partly detoxified during preincubation by
liver S-9 from 3-month-old rats more than by that from 24-month-old rats.
It is suggested that incidence of chemical carcinogenesis may increase
along with aging due to the altered xenobiotics metabolism.
