5-Aminolevulinic acid mediates the in vivo and in vitro formation of 8-hydroxy-2'-deoxyguanosine in DNA.

Abstract:

:5-Aminolevulinic acid (ALA), a heme precursor accumulated in chemical and inborn porphyrias, may behave as an endogenous pro-oxidant. In chronically treated rats (40 mg ALA/kg body wt every 2 days for 15 days) the steady-state level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in liver DNA (94.5 +/- 23.3 residues/10(6) dG) was 4.5 times higher than in non-treated rats (21 +/- 7.5 residues/10(6) dG). In vitro exposure of calf thymus DNA to ALA (0.05-5 mM) in the presence of 10 microM Fe2+ caused the formation of 8-OHdG. The amount of 8-OHdG rose from 135 +/- 15 residues/10(6) dG in the control system to 1140 +/- 150 residues/10(6) dG after incubation with 5 mM ALA and 10 microM Fe2+. Diethylenetriaminepentaacetic acid (5 mM) or mannitol (100 mM) inhibited the formation of 8-OHdG by 63 and 69% respectively, evidencing the involvement of both H2O2 and HO. in this process. Hydrogen peroxide (100 microM) or Fe2+ alone did not cause DNA oxidation. The present data support the hypothesis that ALA-generated reactive oxygen species can oxidize DNA and may be involved in the development of primary liver cell carcinoma in individuals with symptomatic acute intermittent porphyria.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Fraga CG,Onuki J,Lucesoli F,Bechara EJ,Di Mascio P

doi

10.1093/carcin/15.10.2241

subject

Has Abstract

pub_date

1994-10-01 00:00:00

pages

2241-4

issue

10

eissn

0143-3334

issn

1460-2180

journal_volume

15

pub_type

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