The Cooked Meat Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine Hair Dosimeter, DNA Adductomics Discovery, and Associations with Prostate Cancer Pathology Biomarkers

Jingshu Guo, Joseph S. Koopmeiners, Scott J. Walmsley, Peter W Villalta, Lihua Yao, Paari Murugan, Resha D Tejpaul, Christopher J Weight, Robert J. Turesky

Research output: Contribution to journalReview articlepeer-review

Abstract

Well-done cooked red meat consumption is linked to aggressive prostate cancer (PC) risk. Identifying mutation-inducing DNA adducts in the prostate genome can advance our understanding of chemicals in meat that may contribute to PC. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic aromatic amine (HAA) formed in cooked meat, is a potential human prostate carcinogen. PhIP was measured in the hair of PC patients undergoing prostatectomy, bladder cancer patients under treatment for cystoprostatectomy, and patients treated for benign prostatic hyperplasia (BPH). PhIP hair levels were above the quantification limit in 123 of 205 subjects. When dichotomizing prostate pathology biomarkers, the geometric mean PhIP hair levels were higher in patients with intermediate and elevated-risk prostate-specific antigen values than lower-risk values <4 ng/mL (p = 0.03). PhIP hair levels were also higher in patients with intermediate and high-risk Gleason scores ≥7 compared to lower-risk Gleason score 6 and BPH patients (p = 0.02). PC patients undergoing prostatectomy had higher PhIP hair levels than cystoprostatectomy or BPH patients (p = 0.02). PhIP-DNA adducts were detected in 9.4% of the patients assayed; however, DNA adducts of other carcinogenic HAAs, and benzo[a]pyrene formed in cooked meat, were not detected. Prostate specimens were also screened for 10 oxidative stress-associated lipid peroxidation (LPO) DNA adducts. Acrolein 1,N2-propano-2′-deoxyguanosine adducts were detected in 54.5% of the patients; other LPO adducts were infrequently detected. Acrolein adducts were not associated with prostate pathology biomarkers, although DNA adductomic profiles differed between PC patients with low and high-grade Gleason scores. Many DNA adducts are of unknown origin; however, dG adducts of formaldehyde and a series of purported 4-hydroxy-2-alkenals were detected at higher abundance in a subset of patients with elevated Gleason scores. The PhIP hair biomarker and DNA adductomics data support the paradigm of well-done cooked meat and oxidative stress in aggressive PC risk.

Original languageEnglish (US)
Pages (from-to)703-730
Number of pages28
JournalChemical research in toxicology
Volume35
Issue number5
DOIs
StatePublished - May 16 2022

Bibliographical note

Funding Information:
This work was supported by the University of Minnesota Masonic Cancer Center, the National Cancer Institute (R01CA122320, R01CA220367, and R50CA211256), and the National Institute of Environmental Health Sciences (R01ES019564, R03ES031188, and U2CES026533). Mass spectrometry was supported by Cancer Center Support grant CA077598 from the National Cancer Institute, and human biospecimens were supported by the National Center for Advancing Translational Sciences of the National Institutes of Health award number UL1TR000114.

Publisher Copyright:
© 2022 American Chemical Society.

Keywords

  • Acrolein
  • Biomarkers
  • Carcinogens/analysis
  • DNA
  • DNA Adducts
  • Hair/chemistry
  • Humans
  • Male
  • Meat/adverse effects
  • Prostatic Hyperplasia
  • Prostatic Neoplasms
  • Pyridines
  • Radiation Dosimeters

PubMed: MeSH publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural

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