TY - JOUR
T1 - 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
AU - Guo, Jingshu
AU - Koopmeiners, Joseph S.
AU - Walmsley, Scott J.
AU - Villalta, Peter W.
AU - Yao, Lihua
AU - Murugan, Paari
AU - Tejpaul, Resha
AU - Weight, Christopher J.
AU - Turesky, Robert J.
N1 - Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/5/16
Y1 - 2022/5/16
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.chemrestox.2c00012
DO - 10.1021/acs.chemrestox.2c00012
M3 - Review article
C2 - 35446561
AN - SCOPUS:85129260923
SN - 0893-228X
VL - 35
SP - 703
EP - 730
JO - Chemical research in toxicology
JF - Chemical research in toxicology
IS - 5
ER -