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O Hernandez

Publications and source records attributed to O Hernandez.

48 records · Page 3Linked to original sources
PubMed1976

Mutagenicity and cytotoxicity of benzo(a)pyrene benzo-ring epoxides.

Four benzo-ring epoxides of the environmental carcinogen benzo(a)pyrene (BP) were tested for mutagenic and cytotoxic activity in 3 strains of Salmonella typhimurium (TA1538, TA98, and TA100) and in Chinese hamster V79 cells. Although very unstable in aqueous solution, 7beta,8alpha-dihydroxy-0beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol epoxide 1), with the 7-hydroxyl group on the same face of the molecule as the epoxide oxygen, was 1.5 to 4 times as mutagenic in the bacterial strains as was its more stable stereoisomer 7beta,8alpha-dihydroxy-9alpha,10beta-epoxy-7,8,9.10-tetrahydrobenzo(a)pyrene (diol epoxide 2). In V79 cells, diol epoxide 1 had one-third the mutagenic activity of diol epoxide 2 but was at least 10 times more labile than diol epoxide 2 in the tissue culture medium. The half-life of diol epoxide 1 in tissue culture medium was about 30 sec, whereas the half-life of diol epoxide 2 was between 6 and 12 min. 9,10-Epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, which is saturated in the benzo ring, is also very unstable and has mutagenic activity equal to or greater than diol epoxide 1 in the bacterial and mammalian cells. 7,8-Epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene was more stable in aqueous solution than any of the 9,10-epoxides of BP but was much less mutagenic in both the bacterial and mammalian cells. In v79 cells, diol epoxides 1 and 2 and 9,10-opoxy-7,8,9,10-tetrahydrobenzo(a)pyrene were more than 40 times more cytotoxic than 7,8-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene. The mutagenicity of the 2 tetrahydro epoxides toward strain TA98 of S. typhimurium was readily abolished by purified epoxide hydrase, whereas the mutagenic activity of the 2 diol epoxides was relatively unaffected by coincubation with the enzyme.

Animals↗
PubMedDate not supplied

Cytosolic glutathione S-transferases in various rat tissues differ in stereoselectivity with polycyclic arene and alkene oxide substrates.

The stereoselectivity of cytosolic glutathione S-transferases (GS-T) in rat tissues was determined using (+/-)-benzo(a)pyrene 4,5-oxide (BPO), (+/-)-benz(a)anthracene 5,6-oxide (BAO), pyrene 4,5-oxide (PO), and (+/-)-styrene 7,8-oxide (SO) as substrates. An HPLC system is described which separates the four diastereomeric glutathione (GSH) adducts of BPO. Liver, lung, testis, and heart cytosol were found to be highly selective for catalysis of the reaction of the GSH sulfur atom with R-configured oxirane carbon atoms of BPO; heart was the most stereoselective of these tissues with 93% of the products arising from thiol attack at the R-configured carbons. These same tissues showed identical but lower stereoselectivity with PO or BAO as substrate. With SO as substrate, GSH attack was primarily at the benzylic carbon atom of the R-configured enantiomer in all tissues. In contrast, kidney and spleen cytosol were highly stereoselective for reaction of GSH with S-configured oxirane carbon atoms of all three polycyclic arene oxides (R/S ratio = 0.2-0.3) and showed a greater amount of attack at the terminal carbon atom of (7R)-SO. Enantioselectivity of GS-T from these tissues with BPO as substrate varied substantially; liver, kidney, spleen, and intestine preferentially catalyzed reaction with (4R,5S)-BPO (2.8- to 5.1-fold), but testis, lung, and heart showed little or no enantioselectivity [(4R,5S)-BPO/(4S,5R)-BPO = 1.3, 1.3, and 0.96, respectively]. In general, the differences in stereoselectivity between different rat tissues correlate with known tissue differences in isozyme composition and demonstrate that some rat GS-T isozymes may have markedly different stereo- and enantioselectivities with chiral epoxide substrates.

Animals↗
PubMedDate not supplied

The metabolism and excretion of 14C-styrene oxide-glutathione adducts administered to the winter flounder, Pseudopleuronectes americanus, a marine teleost. Identification of the corresponding S-cysteine derivatives as major urinary metabolites.

The metabolism and excretion of intramuscularly administered 14C-glutathione conjugates of styrene oxide (Ia and IIa) were studied in the winter flounder at three dose levels. The various radiolabeled thioether metabolites excreted were separated by reverse-phase high pressure liquid chromatography, and identified and quantitated by cochromatography with synthetic standards. The urine was the major excretion route for radioactivity derived from the glutathione conjugates (up to 90%) at each dose level (1.0, 3.9, and 24.4 mg/fish) studied. The corresponding cysteine derivatives (Ic, IIc) were the major urinary metabolites although the N-acetylcysteine derivatives (Id, IId), or mercapturic acids, were also present in significant amounts at each dose and excretion interval examined. Unchanged glutathione conjugates of styrene oxide were the major radioactive constituents of 24-hr bile samples from the treated flounder, although significant amounts of the cysteinylglycine (Ib, IIb), cysteine, and N-acetylcysteine derivatives were also present in bile. Bile was a minor excretory route relative to urine. The oxidation of 14C-styrene to styrene 7,8-oxide by the cytochrome P-450-dependent monooxygenase system of hepatic microsomes of winter flounder was also demonstrated; likewise, styrene was converted to the diastereomeric glutathione conjugates of styrene 7,8-oxide by 9,000g supernatant fractions of flounder liver supplemented with glutathione. This study demonstrated that flounder liver can convert styrene to glutathione conjugates to styrene oxide and that mercapturic acid biosynthesis occurs after parenteral administration of a xenobiotic-glutathione adduct to this marine species, although the major urinary metabolites were the cysteine conjugates rather than the anticipated mercapturic acid derivatives.

Acetylcysteine↗
PubMedDate not supplied

[Postoperative morbidity/mortality in gastric cancer according to the rules of the Japanese Society: preliminary report].

With the purpose of evaluate the Morbi-mortality related with the kind of surgery recommended by the Japanese Research Society for Gastric Cancer (JRSGC), 13 patients treated surgically by the Rules of that Society were reviewed. Eleven patients were males and 2 females, with ages between 24 and 72 years old. Twelve of them were operated at the Hospital "Dr. Luis Gómez López" (MSAS) and one in a private clinic, both centers located in Barquisimeto, Lara State. Twelve (92.3%) of the patients had advanced Gastric Cancer and only one case was an Early Gastric Cancer. Nine patients received a Distal Gastrectomy (69.23%) and 4 a Total Gastrectomy. Eight among the 13 also underwent a combined resection of another organ(s) (Spleen; 4: Transverse Colon: 1; some kind of Pancreatic resection: 3; Gallbladder: 2). Considering the kind of Radicality (= D2: lymph Node Level Dissection, based on the JRSGC), 10 patients (76.9%) received a D2 type (the Radicality recommended by the JRSGC), being also disected another Lymph Groups (ALFA), and the Paraortics one in 6 of them. The Post-operative Stages founded were: Ia: one case; II:2 cases; IIIb: 3 cases; IV a:2 cases and IVb: 5 cases (38.46%). In relation with the Post-operative Morbidity, directly related with this kind of surgery, only one patient with a severe Desnutrion developed a Fistula, but it healed spontaneously, after a conservative treatment. Two patients received a second surgery; one during the immediate Post-operative period because a Mesentery Rotation, and the other at the 20th. Post-operative day due to an eventration plus an abdominal wall abscess. Both patients were discharge in good conditions. None of the 13 cases stayed in an Intensive or Intermediate Care Unit. There was no case of Post-operative Mortality. It is important to reassure the low risk of Post-operative Complications with this kind of Radical surgery, for Gastric Cancer patients, even in those with nutrional deficit and with a minimal hospital conditions.

Adult↗