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PubMed1992

The ability of liver extracts from different-aged rats to repair 'mis-instructive' and 'non-instructive' lesions of DNA.

The ability to repair 'mis-instructive', O6-methylguanine, and 'non-instructive', AP sites, DNA lesions in Fischer 344 rat livers at various ages was determined. Different behaviours were observed. While the AP-endodesoxyribonuclease enzymes displayed a high constant level throughout the animals' lifetime, the O6-methylguanine-DNA methyltransferase activity presented a stepwise modulation (DNA normalisation of results): the O6-MT activity significantly increased within the first month of animal life and enhanced again after 6 months reaching a maximum plateau in the 12-18-month-old animals. Thereafter a net significant decrease of O6-MT enzyme was detected in the 24-month-old group. While the repair of the widely formed AP sites appeared uniformly efficient like 'house keeping' functions, the removal of the rare precancerous O6-methylguanine is age-dependent indicating a decreased protection of the youngest and oldest animals against this 'mis-instructive' damage. However, any extrapolation of the age-associated cancer risk needs further assessment.

Aging↗
PubMed1984

Selenium suppresses the metabolism of benzo[a]pyrene by rat-liver extracts, and exerts a dual effect on its mutagenicity.

Liver homogenates from rats injected with 3-methylcholanthrene were employed for metabolism of benzo[a]pyrene (BP) and in assays of aryl hydrocarbon hydroxylase (AHH) activity in vitro. Sodium selenite inhibited AHH activity to a maximum of approximately 70%. It suppressed the overall metabolism of benzo[a]pyrene; a distinct reduction in the products was evident on h.p.l.c. analysis. Sodium thiosulphate also inhibited AHH activity by approximately 47%. Inclusion of S2O3(2-) and SeO3(2-), in combination, led to a cumulative inhibition of 87%. The mutagenicity of BP in the Salmonella auxotroph reversion system (Ames test) was enhanced by SeO3(2-) at concentrations below 0.2 mM. Above this level a significant antimutagenic effect was observed.

Animals↗