Aflatoxin B1 DNA-Adducts in Hepatocellular Carcinoma from a Low Exposure Area
Abstract
:1. Introduction
2. Patients and Methods
2.1. Patients
- Cohort 1: 131 surgically resected HCCs were studied by immunohistochemistry (IHC) to determine the presence of AFB1-adducts, mutated TP53 aberrant accumulation, and CD68, to characterize AFB1-adducts positive cells among the tumor-infiltrating cell populations. Restriction fragment length polymorphism (RFLP) analysis of TP53 R249S transversion was performed in a subgroup of 77 patients, while 27 matched HCC and cirrhotic tissues were previously sequenced to detect TP53 gene mutations [13].
- Cohort 2: 45 surgically-resected CC were studied by IHC to determine the presence of AFB1-adducts.
- Cohort 3: 20 explanted end-stage cirrhotic livers were studied by IHC to determine the presence of AFB1 adducts, mutated TP53 aberrant accumulation, CD68 IHC to characterize AFB1 adducts positive cells.
2.2. Rat Model of HCC Exposed to AFB1
2.3. Immunohistochemical Assay of AFB1 Adducts
2.4. Statistical Analysis
3. Results
3.1. AFB1 Adducts Are Present in HCC but Not in CC Tissues
3.2. DNA Adducts Are Present in AFB1-Exposed Rats HCC
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
Statement of Ethics
References
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DNA-Adducts Positive | DNA-Adducts Negative | Significance | |
---|---|---|---|
Hepatocarcinoma (N = 131) | 25/131 (19.1%) | 106/131 (80.9%) | Chi-square, p = 0.048 |
male | 16 (64%) | 89 (84%) | Chi-square, p = 0.07 |
female | 9 (36%) | 17 (16%) | Chi-square, n.s. |
TP53 accumulation | 12 (48%) | 29 (27.4%) | |
Viral infection | 21 (84%) | 79 (74.5%) | |
Non viral | 4 (16%) | 27 (25.5%) | |
HCV | 14 (56%) | 49 (46.2%) | |
HBV | 5 (20%) | 17 (16%) | |
HBV + HCV | 1 (4%) | 6 (5.7%) | |
HBV + HDV | 1 (4%) | 0 | |
metabolic | 3 (12%) | 18 (17%) | |
alcohol | 1 (4%) | 9 (8.5%) | |
HCV + Previous HBV | 0 (0%) | 7 (6.6%) | |
Smoking history | 1/18 * (5.5%) | 12/71 * (16.9%) | Chi-square, n.s. |
Cholangiocarcinoma (N = 45) | 0 | 45 | |
male | 21 | ||
female | 24 | ||
TP53 accumulation | 14 (31%) | ||
Non viral | 40 (88.9%) | ||
HCV | 5 (11.1%) | ||
HBV | 0 | ||
Smoking history | 8/29 * | ||
Liver transplantation (N = 20) | 1/20 | 19/20 | |
male | 1 | 13 | |
female | 0 | 6 | |
TP53 accumulation | 0 | 0 | |
HCV | 1 | 11 | |
HBV | 0 | 3 | |
HBV + HCV | 0 | 1 | |
metabolic | 0 | 3 | |
alcohol | 0 | 1 | |
Smoking history | 0/1 | 3/19 |
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Gramantieri, L.; Gnudi, F.; Vasuri, F.; Mandrioli, D.; Fornari, F.; Tovoli, F.; Suzzi, F.; Vornoli, A.; D’Errico, A.; Piscaglia, F.; et al. Aflatoxin B1 DNA-Adducts in Hepatocellular Carcinoma from a Low Exposure Area. Nutrients 2022, 14, 1652. https://doi.org/10.3390/nu14081652
Gramantieri L, Gnudi F, Vasuri F, Mandrioli D, Fornari F, Tovoli F, Suzzi F, Vornoli A, D’Errico A, Piscaglia F, et al. Aflatoxin B1 DNA-Adducts in Hepatocellular Carcinoma from a Low Exposure Area. Nutrients. 2022; 14(8):1652. https://doi.org/10.3390/nu14081652
Chicago/Turabian StyleGramantieri, Laura, Federica Gnudi, Francesco Vasuri, Daniele Mandrioli, Francesca Fornari, Francesco Tovoli, Fabrizia Suzzi, Andrea Vornoli, Antonia D’Errico, Fabio Piscaglia, and et al. 2022. "Aflatoxin B1 DNA-Adducts in Hepatocellular Carcinoma from a Low Exposure Area" Nutrients 14, no. 8: 1652. https://doi.org/10.3390/nu14081652