Background: Polymorphisms in genes encoding enzymes involved in xenobiotic metabolism and/or in cellular defenses against carcinogen-induced DNA damage play an important role in determining individual cancer susceptibility. However, their distribution and association with cancer susceptibility can vary in different populations.
Materials And Methods: A case-control study including 290 cancer patients (cases) and 242 controls was performed to evaluate the relationship between polymorphisms of cytochrome P450 (CYP)1A1 and CYP2E1 and X-ray repair complementing defective repair in Chinese hamster cells (XRCC)1 genes and the risk of developing cancer in a Southern Italian (Basilicata) population. Genomic DNA was isolated from 5 ml whole blood and genotyping was performed using a PCR-RFLP technique.
Results: No significant differences were observed in the distribution of the CYP1A1, CYP2E1 and XRCC1 gene polymorphisms between the cases and controls in the population under study.
Conclusion: The distribution of CYP1A1, CYP2E1 and XRCC1 gene polymorphisms in the Basilicata population is not different from that of other Italian regions or from that reported in the literature for Caucasian populations, and polymorphisms in these genes do not play an important role in determining cancer risk in the population under study.
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Drug Metab Pharmacokinet
November 2024
Laboratory of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
The previously reported Template system for the prediction of human CYP2B6-mediated reactions (Drug Metab Pharmacokinet 26 309-330, 2011) has been refined with the introduction of ideas of allowable width, Trigger-residue and the residue-initiated movement of ligands in the active site. The refined system also includes ideas of bi-molecule binding on Template. With the use of these ideas in common with other Template systems for human CYP1A1, CYP1A2, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2E1, and CYP3A4, 360 reactions of 261 distinct chemicals reported as CYP2B6 ligands were examined in the refined system.
View Article and Find Full Text PDFToxics
November 2024
The Julius L. Chambers Biomedical/Biotechnology Research Institute (JLC-BBRI), North Carolina Central University (NCCU), Durham, NC 27707, USA.
Crude oil naphtha fraction C9 alkylbenzenes consist of trimethylbenzenes, ethyltoluenes, cumene, and n-propylbenzene. The major fraction of C9 alkylbenzenes is ethyltoluenes (ETs) consisting of three isomers: 2-ethyltoluene (2-ET), 3-ethyltoluene (3-ET), and 4-ethyltoluene (4-ET). Occupational and environmental exposure to ETs can occur via inhalation and ingestion and cause several health problems.
View Article and Find Full Text PDFFood Saf (Tokyo)
December 2024
Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
A Template system for the understanding of human CYP2J2-mediated reactions was constructed from the assembly of the ligands with the introduction of ideas of allowable width, Trigger-residue and the residue-initiated movement of ligands in the active site, which were in common with other Template* systems for human CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2E1, CYP3A4, CYP3A5, and CYP3A7 (Drug Metab Pharmacokinet 2016, 2017, 2019, 2020, 2021, 2022, 2023, 2024, and in press 2024). CYP2J2 system also includes ideas of bi-molecule binding of ligands on the Template. From their placements on the Template and rules for interaction modes, verifications of good and poor substrates, regio/stereo-selectivity, and inhibitory interaction became available faithfully for these ligands.
View Article and Find Full Text PDFChem Res Toxicol
November 2024
Laboratory of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 4228526, Japan.
The prediction of cytochrome P450 inhibition by a computational (quantitative) structure-activity relationship approach using chemical structure information and machine learning would be useful for toxicity research as a simple and rapid tool. However, there are few models focusing on the species differences between rat and human in the P450s inhibition. This study aimed to establish models to classify chemical substances as inhibitors or non-inhibitors of various rat and human P450s, using only molecular descriptors.
View Article and Find Full Text PDFToxins (Basel)
September 2024
Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria.
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