Variability of albumin adducts of 1,4-benzoquinone, a toxic metabolite of benzene, in human volunteers

Abstract

A putative haematotoxic and leukaemogenic metabolite of benzene, 1,4-benzoquinone (1,4-BQ), reacts rapidly with macromolecules. The authors previously characterized levels of the albumin (Alb) adduct (1,4-BQ-Alb) of this reactive species in populations of workers exposed to benzene. Since high levels of 1,4-BQ-Alb were also measured in unexposed workers from those investigations, the current study was initiated to determine potential sources of 1,4-BQ in the general population. A single blood sample was collected from 191 healthy subjects from the Research Triangle area, NC, USA, to determine the baseline 1,4-BQ-Alb levels and contributing sources. The median 1,4-BQ-Alb at baseline was 550 pmol g⁻¹ Alb (interquartile range 435–814 pmol g⁻¹). A second blood sample was collected approximately 3 months later from a subgroup of 33 subjects to estimate the within- and between-person variation in 1,4-BQ-Alb. Standardized questionnaires were administered to collect information about demographic, dietary and lifestyle factors. Multiple linear regression models identified several significant contributors to 1,4-BQ-Alb levels, including gender, body mass index (BMI), the gender–BMI interaction, automobile refuelling, smoking status, and consumption of fruit and the artificial sweetener, aspartame. The authors predicted that these background levels of 1,4-BQ-Alb were equivalent to occupational exposures between 1 and 3 parts per million of benzene. Mixed effects linear models indicated that the random variation in adduct levels was about equally divided between and within subjects. The observations indicate that levels of 1,4-BQ-Alb cover a wide range in the general population, and they support the hypotheses that demographic, diet and lifestyle factors are contributing sources.

Keywords: :

• Background
• benzoquinone
• albumin adducts
• benzene
• variance components

Acknowledgements

Blood was collected with assistance from the General Clinical Research Center, University of North Carolina School of Medicine. The authors are grateful to Christina Martinez, who performed the assays for albumin adducts. They also appreciate the contributions of Qingshan Qu, Roy Shore, Beverley Cohen, Songnian Yin and Guilan Li, who provided data from an earlier investigation of Chinese control workers. The authors received technical assistance regarding sources of dietary phenols from the Nutrition Core of the UNC Center for Environmental Health and Susceptibility. They are also indebted to two anonymous reviewers who noted that several aspects of the findings were not addressed in the original submission. The study was supported in part by a Population Sciences Research Award from the UNC Lineberger Comprehensive Cancer Center, by Grants Nos P42ES05948 and P30ES10126 from the National Institute for Environmental Health Sciences, and by Grant No. R01CA69463 from the National Cancer Institute.