Methanol exposure does not produce oxidatively damaged DNA in lung, liver or kidney of adult mice, rabbits or primates
- Faculty of Pharmacy, University of Toronto, Toronto, Ontario (Canada)
In vitro and in vivo genotoxicity tests indicate methanol (MeOH) is not mutagenic, but carcinogenic potential has been claimed in one controversial long-term rodent cancer bioassay that has not been replicated. To determine whether MeOH could indirectly damage DNA via reactive oxygen species (ROS)-mediated mechanisms, we treated male CD-1 mice, New Zealand white rabbits and cynomolgus monkeys with MeOH (2.0 g/kg ip) and 6 h later assessed oxidative damage to DNA, measured as 8-oxo-2'-deoxyguanosine (8-oxodG) by HPLC with electrochemical detection. We found no MeOH-dependent increases in 8-oxodG in lung, liver or kidney of any species. Chronic treatment of CD-1 mice with MeOH (2.0 g/kg ip) daily for 15 days also did not increase 8-oxodG levels in these organs. These results were corroborated in DNA repair-deficient oxoguanine glycosylase 1 (Ogg1) knockout (KO) mice, which accumulated 8-oxodG in lung, kidney and liver with age, but exhibited no increase following MeOH, despite a 2-fold increase in renal 8-oxodG in Ogg1 KO mice following treatment with a ROS-initiating positive control, the renal carcinogen potassium bromate (KBrO{sub 3}; 100 mg/kg ip). These observations suggest that MeOH exposure does not promote the accumulation of oxidatively damaged DNA in lung, kidney or liver, and that environmental exposure to MeOH is unlikely to initiate carcinogenesis in these organs by DNA oxidation.
- OSTI ID:
- 21535212
- Journal Information:
- Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 250; ISSN TXAPA9; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Significance of cadmium levels in blood and urine during long-term exposure of rats to cadmium
A role for glutathione, independent of oxidative stress, in the developmental toxicity of methanol
Related Subjects
ADULTS
AGE GROUPS
ALCOHOLS
ANIMALS
AUSTRALASIA
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CARCINOGENS
CHEMISTRY
CHROMATOGRAPHY
DAMAGE
DEVELOPED COUNTRIES
DIGESTIVE SYSTEM
DISEASES
DNA
DNA DAMAGES
DNA REPAIR
ELECTROCHEMISTRY
ENVIRONMENTAL EXPOSURE
GLANDS
HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY
HYDROXY COMPOUNDS
IN VITRO
IN VIVO
ISLANDS
KIDNEYS
LIQUID COLUMN CHROMATOGRAPHY
LIVER
LUNGS
MAMMALS
METHANOL
MICE
MONKEYS
NEOPLASMS
NEW ZEALAND
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PRIMATES
RABBITS
REPAIR
RESPIRATORY SYSTEM
RODENTS
SEPARATION PROCESSES
VERTEBRATES