Identification and characterization of 2'-deoxyadenosine adducts formed by isoprene monoepoxides in vitro.

Isoprene, the 2-methyl analogue of 1,3-butadiene, is ubiquitous in the environment, with major contributions to total isoprene emissions stemming from natural processes despite the compound being a bulk industrial chemical. Additionally, isoprene is a combustion product and a major component in cigarette smoke. Isoprene has been classified as possibly carcinogenic to humans (group 2B) by IARC and as reasonably anticipated to be a human carcinogen by the National Toxicology Program.

Synthesis, characterization, and identification of N7-guanine adducts of isoprene monoepoxides in vitro.

Isoprene (IP, 2-methylbuta-1,3-diene) is ubiquitous in the environment through emission by plants, combustion processes, and endogenous formation and exhalation by mammals, including humans. IP is also an industrial chemical, widely used in the manufacture of synthetic rubber and plastics. Like butadiene, IP is metabolized to reactive epoxides, which form adducts with macromolecules, and is a demonstrated carcinogen in mice.

Influence of metabolic genotypes on biomarkers of exposure to 1,3-butadiene in humans.

Carcinogenicity of 1,3-butadiene (BD) has been linked to its metabolic activation of genotoxic epoxides. The inherited variations in the activity of BD-metabolizing enzymes may be responsible for individual differences that modulate the effects of BD exposure. In this study, 40 Italian subjects (30 BD-exposed workers and 10 clerks) were investigated to evaluate the role of genetic polymorphism of cytochromes P450 2E1, microsomal epoxide hydrolase, glutathione transferases GSTM1, GSTP1, GSTT1, and alcohol dehydrogenase, on urinary N-acetyl-S-(3,4-hydroxybutyl)-L-cysteine (MI) and hemoglobin N-(2,3,4-trihydroxybutyl)-valine adducts (THBVal).