Methanol exposure does not produce oxidatively damaged DNA in lung, liver or kidney of adult mice, rabbits or primates

Journal Article · Sat Jan 15 00:00:00 EST 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.10.004· OSTI ID:21535212

McCallum, Gordon P; Siu, Michelle; Sweeting, J Nicole ^[1]

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1. 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, Vol. 250, Issue 2; Other Information: DOI: 10.1016/j.taap.2010.10.004; PII: S0041-008X(10)00380-7; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADULTS
CARCINOGENS
DAMAGE
DNA
DNA DAMAGES
DNA REPAIR
ELECTROCHEMISTRY
ENVIRONMENTAL EXPOSURE
HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY
IN VITRO
IN VIVO
KIDNEYS
LIVER
LUNGS
METHANOL
MICE
MONKEYS
NEOPLASMS
NEW ZEALAND
RABBITS
AGE GROUPS
ALCOHOLS
ANIMALS
AUSTRALASIA
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CHEMISTRY
CHROMATOGRAPHY
DEVELOPED COUNTRIES
DIGESTIVE SYSTEM
DISEASES
GLANDS
HYDROXY COMPOUNDS
ISLANDS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PRIMATES
REPAIR
RESPIRATORY SYSTEM
RODENTS
SEPARATION PROCESSES
VERTEBRATES