Two cytochrome P450 (CYP), CYP1A1 and CYP1A2, cDNA sequences have been isolated and cloned from harp seal (Phoca groenlandica) and grey seal (Halichoerus grypus). EROD, a model substrate for CYP1A, and heterologous antibodies have been employed as a biomarker in marine mammals, however the CYP1A sequences have not been characterised in these two seal species. mRNA was used as the template in RT-PCR, rather than DNA as this indicates transcription of the CYP1A gene in these seal species exposed to environmental contaminants. Harp and grey seal CYP1A1 amino acid sequences exhibited >99% identity and the CYP1A2 sequences were >98% identical. Phylogenetic analyses of the two seal species with other mammalian, and avian CYP1A sequences, showed the CYP1A1 and CYP1A2 sequences clustered with corresponding sequences in other mammalian species. The closest sequences to the seal CYP1As was dog CYP1A. The CYP1A sequence information presented in this study has provided the necessary data for the future production of species-specific probes for the use as biomarkers of environmental contaminant exposure.
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http://dx.doi.org/10.1016/s1532-0456(02)00064-9 | DOI Listing |
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 PDFCells
November 2024
Independent Researcher, 108815 Moscow, Russia.
Background: Cytochromes P450 (CYPs) are heme-containing oxidoreductase enzymes with mono-oxygenase activity. Human CYPs catalyze the oxidation of a great variety of chemicals, including xenobiotics, steroid hormones, vitamins, bile acids, procarcinogens, and drugs.
Findings: In our review article, we discuss recent data evidencing that the same CYP isoform can be involved in both bioactivation and detoxification reactions and convert the same substrate to different products.
Environ Int
December 2024
Department of Analytical, Environmental and Forensic Sciences, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK. Electronic address:
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