5-Hydroxymethyluracil excretion, plasma TBARS and plasma antioxidant vitamins in adriamycin-treated patients.
The thymine oxidative lesion-5-hydroxymethyluracil (HMUra)-was measured in urine collected from cancer patients. These patients all received chemotherapy using Adriamycin. Adriamycin (ADR) intercalates DNA coils and interferes with normal cell metabolism through diverse biochemical mechanisms that may explain its different actions. The anticancer action of ADR could derive from its interaction with topoisomerase II, resulting in DNA nicking followed by DNA fragmentation and apoptosis. Side effects of ADR-mainly its cardiotoxicity-may derive from the fact that ADR generates superoxide and hydroxyl radicals in two ways: redox-cycling and a Haber-Weiss type reaction due to Fe-ADR complexes. The oxygen free radicals, particularly .OH, are thought to be produced by ADR directly in genomic material and attack all its components. 5-Hydroxymethyluracil is a thymine lesion provoked by these attacks, and it has been proposed as a marker of DNA alterations. In this article, we report the results of a study involving 14 cancer patients treated with ADR. We found that urine HMUra is significantly increased by the anticancer therapy (HMUra (nmol/24 h): 74.4 9.46 vs. 96.3 8.74; p < .01), this increase reveals a higher risk of mutagenesis. Our study is the first to show an in vivo alteration of DNA by ADR. Results also show that thiobarbituric acid reactants increase significantly, and that the vitamin levels for retinol and alpha-tocopherol, which are antioxidant vitamins, are lower at the end of chemotherapy. We suggest to supplement these patients with vitamins A and E, and selenium to reduce the side effects of ADR.
Faure
H
H
G.R.E.P.O., Faculté de Médecine-Pharmacie, La Tronche, France.
Coudray
C
C
Mousseau
M
M
Ducros
V
V
Douki
T
T
Bianchini
F
F
Cadet
J
J
Favier
A
A
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000975:Antioxidants / Q000378:metabolism*; D004249:DNA Damage; D004317:Doxorubicin / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010432:Pentoxyl / Q000031:analogs & derivatives* / Q000652:urine; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism*; D014801:Vitamin A / Q000097:blood; D014810:Vitamin E / Q000097:blood; D014815:Vitamins / Q000097:blood*
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D014815:Vitamins; D014801:Vitamin A; D014810:Vitamin E; C008055:5-hydroxymethyluracil; D010432:Pentoxyl; D004317:Doxorubicin