TY - JOUR
T1 - Detection of 2-amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP)-DNA adducts in human pancreatic tissues
AU - Zhu, J.
AU - Rashid, A.
AU - Cleary, K.
AU - Abbruzzese, J. L.
AU - Friess, H.
AU - Takahashi, S.
AU - Shirai, T.
AU - Li, D.
N1 - Funding Information:
The study was supported by a National Institutes of Health (NIH) grant (Grant No. CA98380), a National Institute of Environmental Health Sciences Center grant (Grant No. P30 ES07784), and an NIH Cancer Center core grant (Grant No. CA16672).
PY - 2006/7
Y1 - 2006/7
N2 - Recent epidemiological investigations have observed an association between the consumption of grilled or barbecued meat and an increased risk of pancreatic cancer, suggesting that dietary exposure to heterocyclic aromatic amines (HCA) may contribute to the development of this disease. 2-Amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP) is the most abundant HCA found in well-done and grilled meats. To determine whether HCA-induced DNA damage is present in the human pancreas, immunohistochemistry and computer-assisted image analysis were used to measure PhIP-DNA adducts in 54 normal pancreatic tissues (N) from persons without pancreatic cancer and in 38 normal adjacent pancreatic tissues (A) and in 39 cancer tissues (T) from 68 patients with pancreatic adenocarcinoma. PhIP-DNA adducts were detected in 53 N, 34 A and 39 T samples. Mean values (±SD) of the absorbency for PhIP staining were 0.22±0.04, 0.24±0.04, and 0.24±0.03 for N, A, and T samples, respectively (p=0.004). Using the median absorbency (0.21) of the samples from normal controls as the cut-off, 71% of A and 77% of T tissues, compared with 48% of N tissues, were distributed in the higher range (p=0.009). The odds ratio of pancreatic cancer was 3.4 (95% confidence interval 1.5-7.5, p=0.002) for individuals with a higher level of PhIP-DNA adducts. This is the first report of the detection of PhIP-DNA adducts in human pancreatic tissue samples obtained from patients with unknown exposure to HCA. Although limited by the small sample size, these preliminary results suggest that PhIP exposure may contribute to human pancreatic cancer development.
AB - Recent epidemiological investigations have observed an association between the consumption of grilled or barbecued meat and an increased risk of pancreatic cancer, suggesting that dietary exposure to heterocyclic aromatic amines (HCA) may contribute to the development of this disease. 2-Amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP) is the most abundant HCA found in well-done and grilled meats. To determine whether HCA-induced DNA damage is present in the human pancreas, immunohistochemistry and computer-assisted image analysis were used to measure PhIP-DNA adducts in 54 normal pancreatic tissues (N) from persons without pancreatic cancer and in 38 normal adjacent pancreatic tissues (A) and in 39 cancer tissues (T) from 68 patients with pancreatic adenocarcinoma. PhIP-DNA adducts were detected in 53 N, 34 A and 39 T samples. Mean values (±SD) of the absorbency for PhIP staining were 0.22±0.04, 0.24±0.04, and 0.24±0.03 for N, A, and T samples, respectively (p=0.004). Using the median absorbency (0.21) of the samples from normal controls as the cut-off, 71% of A and 77% of T tissues, compared with 48% of N tissues, were distributed in the higher range (p=0.009). The odds ratio of pancreatic cancer was 3.4 (95% confidence interval 1.5-7.5, p=0.002) for individuals with a higher level of PhIP-DNA adducts. This is the first report of the detection of PhIP-DNA adducts in human pancreatic tissue samples obtained from patients with unknown exposure to HCA. Although limited by the small sample size, these preliminary results suggest that PhIP exposure may contribute to human pancreatic cancer development.
KW - 2-amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP)
KW - DNA adduct
KW - Immunohistochemistry
KW - Pancreatic cancer
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U2 - 10.1080/13547500600667911
DO - 10.1080/13547500600667911
M3 - Article
C2 - 16908439
AN - SCOPUS:33747337034
SN - 1354-750X
VL - 11
SP - 319
EP - 328
JO - Biomarkers
JF - Biomarkers
IS - 4
ER -