Isolation of a novel metabolizing system enriched in phase-II enzymes for short-term genotoxicity bioassays
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, ISSN: 1383-5718, Vol: 413, Issue: 3, Page: 205-217
1998
- 17Citations
- 3Captures
Metric Options: Counts1 Year3 YearSelecting the 1-year or 3-year option will change the metrics count to percentiles, illustrating how an article or review compares to other articles or reviews within the selected time period in the same journal. Selecting the 1-year option compares the metrics against other articles/reviews that were also published in the same calendar year. Selecting the 3-year option compares the metrics against other articles/reviews that were also published in the same calendar year plus the two years prior.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Metrics Details
- Citations17
- Citation Indexes14
- CrossRef14
- 14
- Policy Citations3
- Policy Citation3
- Captures3
- Readers3
Article Description
Murine S9 liver fractions isolated from mice fed 7.5 g kg −1 2(3)- tert -Butyl-4-hydroxyanisole (BHA) for 3 weeks were tested to determine: (a) the profile of both phase-I and phase-II xenobiotic metabolizing enzymes; (b) their ability to induce in vitro covalent binding of some precarcinogens to calf thymus DNA; and (c) their activation in a standard genetic toxicology assay. With regard to phase-I pathway, the S9 fraction expressed various cytochrome P -450-(CYP) (classes 1A1, 1A2, 2B1, 2E1, and 3A)-dependent biotransformation enzymes at levels comparable with those present in murine control liver. For post-oxidative enzymes, the S9 expressed high levels of glutathione S -transferases (up to 12-fold increase), glutathione S -epoxide-transferase (up to 2.6-fold), UDP-glucuronosyl transferase (up to 5.3-fold) and epoxide hydrolase (up to 2.6-fold) activities, as compared to untreated mice. The in vitro DNA binding of the precarcinogenic agents [ 14 C]-1,4-dichlorobenzene, [ 14 C]-1,2-dichlorobenzene and [ 14 C]-1,4-dibromobenzene, mediated by BHA-induced cytosol and/or microsomal preparation, showed an increase in specific activity comparable to that observed with phase-I (PB/ β NF) induced S9. In some instances, covalent binding was even more elevated using the BHA-induced systems as compared with traditional S9 fractions. For example, cytosol derived from BHA-administered mice was able to induce a significant binding to calf thymus DNA up to 26.2-fold increase for [ 14 C]-1,4-dichlorobenzene, while cytosol from PB/ β NF was not. A high mutagenic response on diploid D 7 strain of Saccharomyces cerevisiae as exemplified by a marked induction of mitotic gene conversion and point (reverse) mutation confirmed that BHA-derived S9 fractions activate precarcinogens to final genotoxins. Because a number of chemicals are activated by either oxidative or post-oxidative enzymes, the use of metabolizing biosystems, with an enhanced phase-II pathway, together with classical S9 fractions, can improve the sensitivity of the assay in detecting unknown genotoxins.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S1383571898000059; http://dx.doi.org/10.1016/s1383-5718(98)00005-9; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0032579744&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/9651530; https://linkinghub.elsevier.com/retrieve/pii/S1383571898000059; http://linkinghub.elsevier.com/retrieve/pii/S1383571898000059; http://api.elsevier.com/content/article/PII:S1383571898000059?httpAccept=text/xml; http://api.elsevier.com/content/article/PII:S1383571898000059?httpAccept=text/plain; http://dx.doi.org/10.1016/s1383-5718%2898%2900005-9; https://dx.doi.org/10.1016/s1383-5718%2898%2900005-9
Elsevier BV
Provide Feedback
Have ideas for a new metric? Would you like to see something else here?Let us know