Among the three active aldehyde oxidases in Arabidopsis thaliana leaves (AAO1-3), AAO3, which catalyzes the oxidation of abscisic-aldehyde to abscisic-acid, was shown recently to function as a reactive aldehyde detoxifier. Notably, aao2KO mutants exhibited less senescence symptoms and lower aldehyde accumulation, such as acrolein, benzaldehyde, and 4-hydroxyl-2-nonenal (HNE) than in wild-type leaves exposed to UV-C or Rose-Bengal. The effect of AAO2 expression absence on aldehyde detoxification by AAO3 and/or AAO1 was studied by comparing the response of wild-type plants to the response of single-functioning aao1 mutant (aao1S), aao2KO mutants, and single-functioning aao3 mutants (aao3Ss). Notably, aao3Ss exhibited similar aldehyde accumulation and chlorophyll content to aao2KO treated with UV-C or Rose-Bengal. In contrast, wild-type and aao1S exhibited higher aldehyde accumulation that resulted in lower remaining chlorophyll than in aao2KO leaves, indicating that the absence of active AAO2 enhanced AAO3 detoxification activity in aao2KO mutants. In support of this notion, employing abscisic-aldehyde as a specific substrate marker for AAO3 activity revealed enhanced AAO3 activity in aao2KO and aao3Ss leaves compared to wild-type treated with UV-C or Rose-Bengal. The similar abscisic-acid level accumulated in leaves of unstressed or stressed genotypes indicates that aldehyde detoxification by AAO3 is the cause for better stress resistance in aao2KO mutants. Employing the sulfuration process (known to activate aldehyde oxidases) in wild-type, aao2KO, and molybdenum-cofactor sulfurase (aba3-1) mutant plants revealed that the active AAO2 in WT employs sulfuration processes essential for AAO3 activity level, resulting in the lower AAO3 activity in WT than AAO3 activity in aao2KO.
- Klíčová slova
- Arabidopsis, Rose‐Bengal, UV‐C irradiation, aldehyde oxidase, aldehyde toxicity, reactive aldehydes, senescence, sulfuration,
- MeSH
- aldehydoxidasa metabolismus genetika MeSH
- aldehydy * metabolismus MeSH
- Arabidopsis * metabolismus genetika účinky záření MeSH
- chlorofyl metabolismus MeSH
- kyselina abscisová metabolismus MeSH
- listy rostlin * metabolismus genetika účinky záření MeSH
- mutace MeSH
- proteiny huseníčku * metabolismus genetika MeSH
- regulace genové exprese u rostlin MeSH
- ultrafialové záření * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- AAO3 protein, Arabidopsis MeSH Prohlížeč
- aldehydoxidasa MeSH
- aldehydy * MeSH
- chlorofyl MeSH
- kyselina abscisová MeSH
- proteiny huseníčku * MeSH
The Arabidopsis thaliana aldehyde oxidase 3 (AAO3) catalyzes the oxidation of abscisic aldehyde (ABal) to abscisic acid (ABA). Besides ABal, plants generate other aldehydes that can be toxic above a certain threshold. AAO3 knockout mutants (aao3) exhibited earlier senescence but equivalent relative water content compared with wild-type (WT) during normal growth or upon application of UV-C irradiation. Aldehyde profiling in leaves of 24-day-old plants revealed higher accumulation of acrolein, crotonaldehyde, 3Z-hexenal, hexanal and acetaldehyde in aao3 mutants compared with WT leaves. Similarly, higher levels of acrolein, benzaldehyde, crotonaldehyde, propionaldehyde, trans-2-hexenal and acetaldehyde were accumulated in aao3 mutants upon UV-C irradiation. Aldehydes application to plants hastened profuse senescence symptoms and higher accumulation of aldehydes, such as acrolein, benzaldehyde and 4-hydroxy-2-nonenal, in aao3 mutant leaves as compared with WT. The senescence symptoms included greater decrease in chlorophyll content and increase in transcript expression of the early senescence marker genes, Senescence-Related-Gene1, Stay-Green-Protein2 as well as NAC-LIKE, ACTIVATED-BY AP3/P1. Notably, although aao3 had lower ABA content than WT, members of the ABA-responding genes SnRKs were expressed at similar levels in aao3 and WT. Moreover, the other ABA-deficient mutants [aba2 and 9-cis-poxycarotenoid dioxygenase3-2 (nced3-2), that has functional AAO3] exhibited similar aldehydes accumulation and chlorophyll content like WT under normal growth conditions or UV-C irradiation. These results indicate that the absence of AAO3 oxidation activity and not the lower ABA and its associated function is responsible for the earlier senescence symptoms in aao3 mutant.
- Klíčová slova
- Arabidopsis, abscisic acid, aldehyde oxidase, reactive aldehydes, senescence,
- MeSH
- aldehydoxidasa genetika metabolismus MeSH
- aldehydy metabolismus toxicita MeSH
- Arabidopsis genetika fyziologie MeSH
- chlorofyl metabolismus MeSH
- kyselina abscisová metabolismus MeSH
- listy rostlin genetika fyziologie MeSH
- oxidace-redukce MeSH
- proteiny huseníčku genetika metabolismus MeSH
- regulátory růstu rostlin metabolismus MeSH
- senescence rostlin MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- AAO3 protein, Arabidopsis MeSH Prohlížeč
- aldehydoxidasa MeSH
- aldehydy MeSH
- chlorofyl MeSH
- kyselina abscisová MeSH
- proteiny huseníčku MeSH
- regulátory růstu rostlin MeSH
Temperature passively affects biological processes involved in plant growth. Therefore, it is challenging to study the dedicated temperature signalling pathways that orchestrate thermomorphogenesis, a suite of elongation growth-based adaptations that enhance leaf-cooling capacity. We screened a chemical library for compounds that restored hypocotyl elongation in the pif4-2-deficient mutant background at warm temperature conditions in Arabidopsis thaliana to identify modulators of thermomorphogenesis. The small aromatic compound 'Heatin', containing 1-iminomethyl-2-naphthol as a pharmacophore, was selected as an enhancer of elongation growth. We show that ARABIDOPSIS ALDEHYDE OXIDASES redundantly contribute to Heatin-mediated hypocotyl elongation. Following a chemical proteomics approach, the members of the NITRILASE1-subfamily of auxin biosynthesis enzymes were identified among the molecular targets of Heatin. Our data reveal that nitrilases are involved in promotion of hypocotyl elongation in response to high temperature and Heatin-mediated hypocotyl elongation requires the NITRILASE1-subfamily members, NIT1 and NIT2. Heatin inhibits NIT1-subfamily enzymatic activity in vitro and the application of Heatin accordingly results in the accumulation of NIT1-subfamily substrate indole-3-acetonitrile in vivo. However, levels of the NIT1-subfamily product, bioactive auxin (indole-3-acetic acid), were also significantly increased. It is likely that the stimulation of hypocotyl elongation by Heatin might be independent of its observed interaction with NITRILASE1-subfamily members. However, nitrilases may contribute to the Heatin response by stimulating indole-3-acetic acid biosynthesis in an indirect way. Heatin and its functional analogues present novel chemical entities for studying auxin biology.
- Klíčová slova
- 1-iminomethyl-2-naphthol, Arabidopsis, Heatin, IAN, NIT1-subfamily, PIF4, aldehyde oxidase, chemical genetics, indole-3-acetonitrile, nitrilases, thermomorphogenesis,
- MeSH
- aldehydoxidasa genetika metabolismus MeSH
- aminohydrolasy genetika metabolismus MeSH
- apomorfin analogy a deriváty farmakologie MeSH
- Arabidopsis účinky léků růst a vývoj MeSH
- herbicidy farmakologie MeSH
- hypokotyl účinky léků růst a vývoj MeSH
- inhibitory enzymů aplikace a dávkování chemie farmakologie MeSH
- kyseliny indoloctové MeSH
- molekulární struktura MeSH
- pikloram farmakologie MeSH
- proteiny huseníčku genetika metabolismus MeSH
- regulace genové exprese u rostlin účinky léků MeSH
- transkriptom účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 10,11-dihydroxy-N-n-propylnorapomorphine MeSH Prohlížeč
- AAO1 protein, Arabidopsis MeSH Prohlížeč
- aldehydoxidasa MeSH
- aminohydrolasy MeSH
- apomorfin MeSH
- herbicidy MeSH
- inhibitory enzymů MeSH
- kyseliny indoloctové MeSH
- nitrilase MeSH Prohlížeč
- pikloram MeSH
- proteiny huseníčku MeSH
Capillary electrophoresis is a modern separation technique characterized by many benefits, which qualify it also for enzyme assays and the study of enzyme kinetics during drug development. Homogeneous or heterogeneous approaches can be followed for the enzymatic incubation. In this study, an immobilization procedure of aldehyde oxidase on magnetic particles was developed considering their integration with capillary electrophoresis. A number of magnetic nano/microparticle types were tested for this purpose, showing that aldehyde oxidase was most active when immobilized on bare silica magnetic nanoparticles. Primarily, the reusability of the enzyme immobilized on bare silica nanoparticles was tested. Three consecutive incubations with substrate could be performed, but the activity considerably dropped after the first incubation. One reason could be an enzyme detachment from the nanoparticles, but no release was detected neither at 4°C nor at 37°C during 5 h. The drop in enzymatic activity observed in consecutive incubations, could also be due to inactivation of the enzyme over time at given temperature. For the immobilized enzyme stored at 4°C, the activity decreased to 83% after 5 h, in contrast with a steep decrease at 37°C to 37%.
- Klíčová slova
- aldehyde oxidase, capillary electrophoresis, enzyme immobilization, magnetic nanoparticles, micellar electrokinetic chromatography,
- MeSH
- aldehydoxidasa analýza metabolismus MeSH
- elektroforéza kapilární MeSH
- enzymatické testy * MeSH
- enzymy imobilizované analýza metabolismus MeSH
- teplota MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- aldehydoxidasa MeSH
- enzymy imobilizované MeSH
BACKGROUND: The aim of our study was to identify the genetic background of thiopurine-induced toxicity in a patient with a wild-type thiopurine methyltransferase genotype and activity. A 38-year-old Caucasian woman presented with cutaneous necrotizing vasculitis pancytopenia one month after starting azathioprine therapy. METHODS: During a routine biochemical follow-up of the patient, undetectable serum uric acid (<10 μl) was observed. A high performance liquid chromatography analysis of urinary purines revealed increased levels of xanthine (137 mmol/mol creatinine). The suspected diagnosis of hereditary xanthinuria, a rare autosomal recessive disorder of the last two steps of purine metabolism, was confirmed by sequence analysis. RESULTS: An analysis of XDH/XO and AOX1 revealed common polymorphisms, while analysis of the MOCOS gene identified a rare homozygous variant c.362C > T. Dysfunction of this variant was confirmed by significantly decreased xanthine dehydrogenase/oxidase activity in the patient's plasma (<2% of control mean activity). CONCLUSIONS: We present a biochemical, enzymatic, and molecular genetic case study suggesting an important association between a hitherto undescribed dysfunction variant in the MOCOS gene and thiopurine-induced toxicity. The identified variant c.362C > T results in slower thiopurine metabolism caused by inhibition of 6-mercaptopurine oxidation (catabolism) to 6-thioxanthine and 6-thiouric acid, which increases the formation of the nucleotide 6-thioguanine, which is toxic. This is the first clinical case to identify the crucial role of the MOCOS gene in thiopurine intolerance and confirm the impact of genetic variability of purine enzymes on different therapeutic outcomes in patients undergoing thiopurine treatment.
- Klíčová slova
- Azathioprine, Human molybdenum cofactor sulfurase, Hypouricemia, Thiopurine-induced toxicity, Xanthinuria,
- MeSH
- aldehydoxidasa nedostatek genetika MeSH
- dospělí MeSH
- kyselina močová krev MeSH
- lidé MeSH
- merkaptopurin škodlivé účinky analogy a deriváty metabolismus MeSH
- methyltransferasy genetika MeSH
- polymorfismus genetický genetika MeSH
- poruchy metabolismu purinů a pyrimidinů genetika MeSH
- sulfurtransferasy genetika MeSH
- xanthin moč MeSH
- xanthindehydrogenasa nedostatek genetika MeSH
- xanthinoxidasa genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aldehydoxidasa MeSH
- AOX1 protein, human MeSH Prohlížeč
- azathiopurine MeSH Prohlížeč
- kyselina močová MeSH
- merkaptopurin MeSH
- methyltransferasy MeSH
- MOCOS protein, human MeSH Prohlížeč
- sulfurtransferasy MeSH
- TPMT protein, human MeSH Prohlížeč
- xanthin MeSH
- xanthindehydrogenasa MeSH
- xanthinoxidasa MeSH
Hereditary xanthinuria (type I) is caused by an inherited deficiency of the xanthine oxidorectase (XDH/XO), and is characterized by very low concentration of uric acid in blood and urine and high concentration of urinary xanthine, leading to urolithiasis. Type II results from a combined deficiency of XDH/XO and aldehyde oxidase. Patients present with hematuria, renal colic, urolithiasis or even acute renal failure. Clinical symptoms are the same for both types. In a third type, clinically distinct, sulfite oxidase activity is missing as well as XDH/XO and aldehyde oxidase. The prevalence is not known, but about 150 cases have been described so far. Hypouricemia is sometimes overlooked, that´s why we have set up the diagnostic flowchart. This consists of a) evaluation of uric acid concentrations in serum and urine with exclusion of primary renal hypouricemia, b) estimation of urinary xanthine, c) allopurinol loading test, which enables to distinguish type I and II; and finally assay of xanthine oxidoreductase activity in plasma with molecular genetic analysis. Following this diagnostic procedure we were able to find first patients with hereditary xanthinuria in our Czech population. We have detected nine cases, which is one of the largest group worldwide. Four patients were asymptomatic. All had profound hypouricemia, which was the first sign and led to referral to our department. Urinary concentrations of xanthine were in the range of 170-598 mmol/mol creatinine (normal < 30 mmol/mol creatinine). Hereditary xanthinuria is still unrecognized disorder and subjects with unexplained hypouricemia need detailed purine metabolic investigation.
- Klíčová slova
- hereditary xanthinuria, hypouricemia, xanthine oxidoreductase deficiency,
- MeSH
- aldehydoxidasa krev nedostatek moč MeSH
- alopurinol metabolismus MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- dospělí MeSH
- kyselina močová krev moč MeSH
- lidé MeSH
- močové kameny krev epidemiologie moč MeSH
- poruchy metabolismu purinů a pyrimidinů krev diagnóza epidemiologie moč MeSH
- předškolní dítě MeSH
- puriny metabolismus MeSH
- vrozené poruchy metabolismu krev diagnóza epidemiologie moč MeSH
- vrozené poruchy tubulárního transportu krev epidemiologie moč MeSH
- xanthin krev moč MeSH
- xanthindehydrogenasa krev nedostatek metabolismus moč MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Názvy látek
- aldehydoxidasa MeSH
- alopurinol MeSH
- kyselina močová MeSH
- puriny MeSH
- xanthin MeSH
- xanthindehydrogenasa MeSH
2-Nitroanisole (2-NA) is an important industrial pollutant and a potent bladder carcinogen for rodents. The mechanism of its carcinogenicity was investigated in this study. Here we have used two independent methods, (32)P-post-labeling and (3)H-labeled 2-NA, to show that 2-NA binds covalently to DNA in vitro after reductive activation by human hepatic cytosol and xanthine oxidase (XO). We also investigated the capacity of 2-NA to form DNA adducts in vivo. Male Wistar rats were treated i.p. with 2-NA (0.15 mg/kg body wt daily for 5 days) and DNA from several organs was analyzed by (32)P-post-labeling. Two 2-NA-specific DNA adducts, identical to those found in DNA incubated with 2-NA and human hepatic cytosol or XO in vitro, were detected in the urinary bladder (3.4 adducts/10(7) nt), the target organ, and, to a lesser extent, in liver, kidney and spleen. The two DNA adducts found in rat tissues in vivo were identified as deoxyguanosine adducts derived from a 2-NA reductive metabolite, N-(2-methoxyphenyl)hydroxylamine. This reactive metabolite of 2-NA was identified in incubations with human hepatic cytosol, besides 2-methoxyaniline (o-anisidine). The results of our study, the first report on the potential of human cytosolic enzymes to contribute to the activation of 2-NA by nitroreduction, strongly suggest a carcinogenic potency of this rodent carcinogen for humans.
- MeSH
- adukty DNA * MeSH
- aldehydoxidasa metabolismus MeSH
- aniliny metabolismus MeSH
- anisoly farmakokinetika toxicita MeSH
- cytosol enzymologie MeSH
- dítě MeSH
- DNA metabolismus MeSH
- dospělí MeSH
- izotopy fosforu * MeSH
- játra účinky léků enzymologie MeSH
- karcinogeny farmakokinetika toxicita MeSH
- krysa rodu Rattus MeSH
- ledviny účinky léků enzymologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- močový měchýř účinky léků enzymologie MeSH
- NAD(P)H dehydrogenasa (chinon) metabolismus MeSH
- potkani Wistar MeSH
- předškolní dítě MeSH
- senioři MeSH
- slezina účinky léků enzymologie MeSH
- xanthinoxidasa metabolismus MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- krysa rodu Rattus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 2-anisidine MeSH Prohlížeč
- 2-nitroanisole MeSH Prohlížeč
- adukty DNA * MeSH
- aldehydoxidasa MeSH
- aniliny MeSH
- anisoly MeSH
- DNA MeSH
- izotopy fosforu * MeSH
- karcinogeny MeSH
- NAD(P)H dehydrogenasa (chinon) MeSH
- NQO1 protein, human MeSH Prohlížeč
- xanthinoxidasa MeSH
Aristolochic acid (AA), a naturally occurring nephrotoxin and carcinogen, has been associated with the development of urothelial cancer in humans. Understanding which human enzymes are involved in AA metabolism is important in the assessment of an individual's susceptibility to this carcinogen. Using the 32P-postlabeling assay we examined the ability of enzymes of cytosolic samples from 10 different human livers and from one human kidney to activate the major component of the plant extract AA, 8-methoxy- 6-nitro-phenanthro-(3,4-d)-1,3-dioxolo-5-carboxylic acid (AAI), to metabolites forming adducts in DNA. Cytosolic fractions of both organs generated AAI-DNA adduct patterns reproducing those found in renal tissues from humans exposed to AA. 7-(Deoxyadenosin-N6-yl)aristolactam I, 7-(deoxyguanosin-N2-yl)aristolactam I and 7-(deoxyadenosin-N6-yl)aristolactam II, indicating a possible demethoxylation reaction of AAI, were identified as AA-DNA adducts formed from AAI by all human hepatic and renal cytosols. To define the role of human cytosolic reductases in the activation of AAI, we investigated the modulation of AAI-DNA adduct formation by cofactors or selective inhibitors of the NAD(P)H:quinone oxidoreductase (NQO1), xanthine oxidase (XO) and aldehyde oxidase. We also determined whether the activities of NQO1 and XO in different human hepatic cytosolic samples correlated with the levels of AAI-DNA adducts formed by the same cytosolic samples. Based on these studies, we attribute most of the activation of AA in human cytosols to NQO1, although a role of cytosolic XO cannot be ruled out. With purified NQO1 from rat liver and kidney and XO from buttermilk, the major role of NQO1 in the formation of AAI-DNA adducts was confirmed. The orientation of AAI in the active site of human NQO1 was predicted from molecular modeling based on published X-ray structures. The results demonstrate for the first time the potential of human NQO1 to activate AAI by nitroreduction.
- MeSH
- adukty DNA analýza MeSH
- aldehydoxidasa metabolismus MeSH
- biotransformace MeSH
- cytosol enzymologie MeSH
- inhibitory enzymů metabolismus MeSH
- játra enzymologie MeSH
- karcinogeny chemie metabolismus farmakokinetika MeSH
- krysa rodu Rattus MeSH
- kyseliny aristolochové chemie metabolismus farmakokinetika MeSH
- ledviny enzymologie MeSH
- lidé MeSH
- molekulární modely MeSH
- NAD(P)H dehydrogenasa (chinon) analýza antagonisté a inhibitory metabolismus MeSH
- potkani Wistar MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- xanthinoxidasa analýza antagonisté a inhibitory metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- adukty DNA MeSH
- aldehydoxidasa MeSH
- aristolochic acid C MeSH Prohlížeč
- aristolochic acid I MeSH Prohlížeč
- inhibitory enzymů MeSH
- karcinogeny MeSH
- kyseliny aristolochové MeSH
- NAD(P)H dehydrogenasa (chinon) MeSH
- NQO1 protein, human MeSH Prohlížeč
- xanthinoxidasa MeSH
Aristolochic acid (AA), a naturally occurring nephrotoxin and rodent carcinogen, has recently been associated with the development of urothelial cancer in humans. Understanding which enzymes are involved in AA activation and/or detoxication is important in the assessment of an individual susceptibility to this natural carcinogen. We examined the ability of enzymes of rat renal and hepatic cytosolic fractions to activate AA to metabolites forming DNA adducts by the nuclease P1-enhanced version of the (32)P-postlabeling assay. Cytosolic fractions of both these organs generated AA-DNA adduct patterns reproducing those found in renal tissues from humans exposed to AA. 7-(Deoxyadenosin-N(6)-yl)aristolactam I, 7-(deoxyguanosin-N(2)-yl)aristolactam I and 7-(deoxyadenosin-N(6)-yl)aristolactam II were identified as AA-DNA adducts formed from AAI and 7-(deoxyguanosin-N(2)-yl)aristolactam II and 7-(deoxyadenosin-N(6)-yl)aristolactam II were generated from AAII by hepatic cytosol. Qualitatively the same AA-DNA adduct patterns were observed, although at lower levels, upon incubation of AAs with renal cytosol. To define the role of cytosolic reductases in the reductive activation of AA, we investigated the modulation of AA-DNA adduct formation by cofactors, specific inducers or selective inhibitors of the cytosolic reductases, DT-diaphorase, xanthine oxidase (XO) and aldehyde oxidase. The role of the enzymes in AA activation was also investigated by correlating the DT-diaphorase- and XO-dependent catalytic activities in cytosolic sample with the levels of AA-DNA adducts formed by the same cytosolic sample. On the basis of these studies, we attribute most of the cytosolic activation of AA to DT-diaphorase, although a role of cytosolic XO cannot be ruled out. With purified DT-diaphorase, the participation of this enzyme in the formation of AA-DNA adducts was confirmed. The binding orientation of AAI in the active site of DT-diaphorase was predicted by computer modeling based on published X-ray structures. The results presented here are the first report demonstrating a reductive activation of carcinogenic AAs by DT-diaphorase.
- MeSH
- adukty DNA * MeSH
- aktivace enzymů MeSH
- aldehydoxidasa MeSH
- aldehydoxidoreduktasy metabolismus MeSH
- buněčné jádro metabolismus MeSH
- časové faktory MeSH
- chemické modely MeSH
- cytosol metabolismus MeSH
- DNA metabolismus MeSH
- fenantreny farmakologie MeSH
- játra metabolismus MeSH
- karcinogeny * MeSH
- komplementární DNA metabolismus MeSH
- krysa rodu Rattus MeSH
- kyseliny aristolochové * MeSH
- léky rostlinné čínské škodlivé účinky MeSH
- molekulární modely MeSH
- NAD(P)H dehydrogenasa (chinon) metabolismus MeSH
- nefritida etiologie metabolismus MeSH
- potkani Wistar MeSH
- protinádorové látky farmakologie MeSH
- thymus metabolismus MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- xanthinoxidasa metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adukty DNA * MeSH
- aldehydoxidasa MeSH
- aldehydoxidoreduktasy MeSH
- aristolochic acid I MeSH Prohlížeč
- DNA MeSH
- fenantreny MeSH
- karcinogeny * MeSH
- komplementární DNA MeSH
- kyseliny aristolochové * MeSH
- léky rostlinné čínské MeSH
- NAD(P)H dehydrogenasa (chinon) MeSH
- protinádorové látky MeSH
- xanthinoxidasa MeSH
