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L Recio

Publications and source records attributed to L Recio.

65 records · Page 4Linked to original sources
PubMed1986

Effects of morphine on noradrenaline release from cerebral and peripheral vascular smooth muscle.

Morphine reduced the [3H]noradrenaline uptake in cat cerebral and femoral arteries and induced a dose-dependent tritium release from these vessels prelabelled with this amine, which was diminished in Ca2+-free medium. The opioid decreased the radioactivity release induced by electrical field stimulation as well as its potentiation by tetraethylammonium. These effects were unaffected by naloxone. These results indicate: the reduction by morphine of tritium release from both kinds of vessels is through a mechanism unrelated to opiate receptors, and the noradrenaline release elicited by morphine could be due in part to inhibition of its reuptake.

Animals↗
PubMed1986

Evidence for reactive oxygen species inducing mutations in mammalian cells.

We have studied the mutagenicity (by selecting for mutants resistant to 6-thioguanine) and cytotoxicity (by determining cellular cloning efficiency) of physical and chemical agents in Chinese hamster ovary (CHO) cells, clone CHO-K1-BH4 (K1-BH4), and its radiation-hypersensitive transformant, AS52. AS52 cells contain a single functional copy of a bacterial gene, the xanthine/guanine phosphoribosyltransferase (gpt) gene instead of its mammalian equivalent, the hypoxanthine/guanine phosphoribosyltransferase (hprt) gene. We found that x-ray and neutron irradiations are equally toxic to both cell types; however, these physical agents are approximately equal to 10 times more mutagenic to AS52 cells than to K1-BH4 cells. Our earlier studies using Southern blot analysis showed that x-irradiation produces mostly or exclusively deletion mutations in both cell types. If reactive oxygen species mediate the mutagenic effects of radiations and chemicals, then radiomimetic compounds such as streptonigrin and bleomycin, which exert their biological effects via reactive oxygen species, and oxidizing compounds such as potassium superoxide and hydrogen peroxide should elicit a similar differential mutagenic response in both cell types. On the other hand, agents such as ethyl methanesulfonate, ICR 191, and UV light, which do not produce reactive oxygen species, should not elicit differential mutagenicity. Our results fulfill such predictions. The apparent hypermutability of AS52 cells probably results from a higher recovery of multilocus deletion mutants in AS52 cells than in K1-BH4 cells, rather than a higher yield of induced mutants.

Animals↗
PubMed1985

Effect of tetraethylammonium and verapamil on noradrenaline release induced by field electrical stimulation and potassium from cat cerebral and femoral arteries.

Tritium release evoked by field electrical stimulation (FES) or high potassium (K+) from cat cerebral and femoral arteries prelabelled with 3H-noradrenaline was investigated. The release induced by FES and K+ was reduced by Ca2+ suppression and tetrodotoxin (TTX) but not by verapamil in both vessels. Tetraethylammonium (TEA) increased tritium release evoked by FES and K+, when TTX plus TEA were added together radioactivity secretion induced by FES was practically abolished. These results indicate that FES or K+ induce exocytotic noradrenaline release mainly by propagated action potentials and by similar mechanisms in cerebral and femoral arteries.

Animals↗
PubMed1984

Glucuronide conjugation reduces the cytotoxicity but not the mutagenicity of benzo(a)pyrene in the CHO/HGPRT assay.

Benzo(a)pyrene (B[a]P) is biotransformed by the mixed-function oxidase (MFO) system to numerous metabolites some of which are cytotoxic and/or mutagenic to mammalian cells. However, conjugation of B(a)P metabolites with glucuronic acid in vivo is a major pathway of detoxication and elimination. The effects of glucuronide conjugation on B(a)P-induced cytotoxicity and mutagenicity were studied using the CHO/HGPRT assay with a rat liver homogenate preparation containing MFO system cofactors (S9 mix) and uridine diphosphate alpha-D-glucuronic acid (UDPGA). B(a)P metabolites proximate to the biologically active B(a)P quinones (B[a]P 6-OH) and to the B(a)P 7,8-diol-9,10 epoxide isomers (B[a]P 7,8-diol), were also assayed with S9 mix in the absence and presence of UDPGA. The addition of UDPGA to S9 mix reduced B(a)P-induced cytotoxicity but did not affect mutagenicity. B(a)P 6-OH-mediated cytotoxicity was also reduced in the presence of UDPGA. UDPGA had no effect on B(a)P 7,8-diol-induced cytotoxicity or mutagenicity. B(a)P phenols have been shown to be the preferred B(a)P-metabolite substrates for UDP-glucuronyltransferase enzymes. Thus, the reduction of B(a)P and B(a)P 6-OH-induced cytotoxicity by glucuronide conjugation is likely due to the elimination of cytotoxic phenols and quinones. Since B(a)P 7,8-diol is a poor substrate for UDP-glucuronyltransferase enzymes, no effects on B(a)P-induced mutagenicity or B(a)P 7,8-diol-induced cytotoxicity and mutagenicity were observed.

Animals↗
PubMed1984

Application of urine mutagenicity to monitor coal liquefaction workers.

The Salmonella/microsomal assay was used to monitor workers' urine for mutagenicity as a potential indicator of human exposure to mutagens/carcinogens. Urine samples from 57 workers at a coal liquefaction pilot plant in Catlettsburg, Kentucky, were assayed for mutagenicity during work periods. Urine samples were collected twice during plant operations and once when the individuals were away from the plant for at least 48 h. In 7 individual smokers (5 operator/maintenance workers and 2 administrative staff workers) there was an indication of enhanced urine mutagenicity during work periods. Urine mutagenicity of nonsmokers from the pilot plant was significantly higher than that of an additional control group of nonsmokers from Lexington, Kentucky. While cigarette smoking was the major factor affecting urine mutagenicity, no significant mutagenicity that could be directly attributed to the pilot plant workers' environment was evident.

Animals↗
PubMed1982

Effect of pentobarbital on the noradrenaline release induced by drugs and field electrical stimulation from cerebral and femoral arteries of the cat.

The present studies showed that field electrical stimulation, high potassium (K+), tyramine and ionophore X537A induced tritium release from cerebral and femoral arteries of cat prelabelled with [3H]noradrenaline. The secretion caused by K+ or field stimulation was CA2+-dependent and was antagonized by high concentrations of pentobarbital (10(-4) and 10(-3) M), whereas that induced by the rest of the drugs was unchanged in the same situations. The noradrenaline uptake by these arteries was reduced by pentobarbital (10(-3) M and 10(-4) M). These results suggest that this barbiturate interferes with Ca2+ entry to the adrenergic nerve endings, and therefore antagonizes the noradrenaline release by Ca2+-dependent processes (exocytosis).

Animals↗
PubMed1982

Parameters affecting the mutagenic activity of cigarette smokers' urine.

Cigarette smoke is a complex chemical mixture which displays a number of biological activities including mutagenesis. The absorption of smoke components by the lungs results in their systemic distribution, which then leads to the presence of mutagens in the urine. The detection of mutagenic substances in the urine by short-term bioassays has been suggested for use in monitoring human exposure to various carcinogenic/mutagenic substances. In this connection, we felt that further studies on the mutagenic activity present in cigarette smokers' urine were needed. In the present studies, the dose-response relationship between the number of cigarettes smoked versus urine mutagenic activity and the persistence of mutagens in the urine after the cessation of smoking have been examined. The studies were carried out on a group of smokers and non-smokers in Lexington, Kentucky. Although a dose-response relationship (urine mutagenicity versus the number of cigarettes smoked per day) was not observed in the group of smokers assayed, a linear dose-response relationship was detected in an individual smoker who smoked a varying number of cigarettes over eight successive days. In another smoker who ceased smoking, mutagens were detected in the urine for one week. The urine mutagenicity data from a group of smokers and non-smokers should prove useful in extending this technique to the monitoring of other environmental exposure.

Adult↗
PubMed1981

Co-mutagenic effects of 2-aminoanthracene and cigarette smoke condensate on smoker's urine in the Ames Salmonella assay system.

Cigarette smoke condensate (CSC) and cigarette smoker's urine (concentrated) (UC) were tested alone and in combination with direct and indirect mutagens for histidine reversion in the Ames Salmonella assay system. While both CSC and smoker's urine showed some mutagenic activity upon metabolic activation with S9-mix, each of them in combination with the aromatic amine 2-aminoanthracene (2AA) exhibited a synergistic effect on mutagenicity. Such a synergistic effect was not found when these agents were combined with the direct mutagens, ethylmethane sulfonate (EMS) and methylmethane sulfonate (MMS), or the indirect mutagens, benzo[a]pyrene (BP) and 9,10-dimethyl-1,2-benzanthracene (DMBA), tested in this study, nor was the synergistic effect observed when 2AA was tested with urine from a non-smoker. The results, thus, reflected a specificity of the co-mutagenic action of factor(s) in cigarette smoke or smoker's urine and 2AA. The significance of co-mutagens in carcinogenesis has been discussed and the importance of investigating co-mutagenesis particularly in the case of suspected human exposure to multiple environmental agents has been emphasized.

Anthracenes↗
PubMedDate not supplied

Use of transgenic animals for carcinogenicity testing: considerations and implications for risk assessment.

Advances in genetic engineering have created opportunities for improved understanding of the molecular basis of carcinogenesis. Through selective introduction, activation, and inactivation of specific genes, investigators can produce mice of unique genotypes and phenotypes that afford insights into the events and mechanisms responsible for tumor formation. It has been suggested that such animals might be used for routine testing of chemicals to determine their carcinogenic potential because the animals may be mechanistically relevant for understanding and predicting the human response to exposure to the chemical being tested. Before transgenic and knockout mice can be used as an adjunct or alternative to the conventional 2-year rodent bioassay, information related to the animal line to be used, study design, and data analysis and interpretation must be carefully considered. Here, we identify and review such information relative to Tg.AC and rasH2 transgenic mice and p53+/- and XPA-/- knockout mice, all of which have been proposed for use in chemical carcinogenicity testing. In addition, the implications of findings of tumors in transgenic and knockout animals when exposed to chemicals is discussed in the context of human health risk assessment.

Animals↗
PubMedDate not supplied

Modulative effects of metabolic effectors on benzo(a)pyrene-induced cytotoxicity and mutagenicity in mammalian cells.

Conjugation and detoxification of mixed function oxidase (MFO)-mediated benzo(a)pyrene [B(a)P] metabolites with glucuronic acid and glutathione (GSH) are major pathways of B(a)P elimination and ultimately excretion in vivo. We have studied the effects of uridine diphosphate alpha-D-glucuronic acid (UDPGA) and GSH, a cofactor for the synthesis of glucuronide and GSH conjugates, respectively, on B(a)P-induced cytotoxicity and mutagenicity in mammalian cells. The S9-mix used in the Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyltransferase (CHO/HPRT) mutational assay was supplemented with either UDPGA, GSH, or GSH plus purified GSH-S-transferases (GSHTs), to study modulation of glucuronide and GSH detoxification mechanisms on B(a)P-induced cytotoxic and mutagenic effects. We found that the addition of UDPGA to S9-mix reduces cytotoxicity induced by either B(a)P or B(a)P 6-OH but not by B(a)P 7,8-diol [B(a)P-diol]. The reduction of B(a)P and B(a)P 6-OH-induced cytotoxicity by glucuronide conjugation is likely due to elimination of cytotoxic phenols and quinones. The addition of GSH to the S9-mix resulted in a reduction of B(a)P- and B(a)P-diol-induced cytotoxicity. GSH plus GSHT reduced B(a)P-induced cytotoxicity and mutagenicity. GSH inhibited the mutagenicity at low concentrations of B(a)P-diol. GSH plus GSHTs inhibited the cytotoxicity and mutagenicity of B(a)P-diol at concentrations not affected by GSH alone. These studies demonstrate that mechanisms of detoxification can affect the biological activity of B(a)P and B(a)P-diol as profoundly as bioactivation by the MFO system. Future research should address studies of mutagenicity modulation by metabolic effectors at both the molecular (DNA sequence) and cellular (quantitative mutagenesis) level.

Animals↗