Comparative enhancing effects of phenobarbital, amobarbital, diphenylhydantoin, and dichlorodiphenyltrichloroethane on 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat.
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Earlier studies showed that phenobarbital feeding enhanced hepatic tumorigenesis in rats previously fed 2-acetylaminofluorene for a brief period. As part of an investigation of the mechanism of this enhancement, the present study evaluated the relative enhancing abilities of amobarbital, diphenylhydantoin, and dichlorodiphenyltrichloroethane (DDT), agents that resemble phenobarbital to varying degrees in their effects on liver structure and metabolism. A comparison of hepatic tumor yields in rats fed 2-acetylaminofluorene, followed by the test substance (sequential treatment), showed that amobarbital and diphenylhydantoin had no enhancing activity, whereas the enhancing effect of DDT was similar to that of phenobarbital. These results show that the sequential treatment technique readily distinguishes among substances differing in enhancing ability and should prove useful in screening additional substances for this activity. The comparative biochemical effects of these substances in the liver can then be correlated with their relative enhancing abilities to provide information on the molecular events specifically associated with enhancement. Such correlations were initiated in this study by comparing the effects of the four test substances on liver weight and DNA synthesis. The results showed that the enhancers, phenobarbital and DDT, each stimulated liver DNA synthesis and increased liver weight, whereas the nonenhancers, amobarbital and diphenylhydantoin, had neither effect. Phenobarbital and DDT both increased the early tumor incidence rate and maintained an increment in tumor incidence over that in the other treatment groups throughout the experiment, although it is not clear whether this increment would persist indefinitely. In addition, although the spectrum of tumor types observed ranged from highly differentiated to poorly differentiated in all treatment groups, DDT and phenobarbital selectively increased the incidence of highly differentiated tumors throughout most of the experiment. (+info)
Identification of a novel class of insect glutathione S-transferases involved in resistance to DDT in the malaria vector Anopheles gambiae.
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The sequence and cytological location of five Anopheles gambiae glutathione S-transferase (GST) genes are described. Three of these genes, aggst1-8, aggst1-9 and aggst1-10, belong to the insect class I family and are located on chromosome 2R, in close proximity to previously described members of this gene family. The remaining two genes, aggst3-1 and aggst3-2, have a low sequence similarity to either of the two previously recognized classes of insect GSTs and this prompted a re-evaluation of the classification of insect GST enzymes. We provide evidence for seven possible classes of insect protein with GST-like subunits. Four of these contain sequences with significant similarities to mammalian GSTs. The largest novel insect GST class, class III, contains functional GST enzymes including two of the A. gambiae GSTs described in this report and GSTs from Drosophila melanogaster, Musca domestica, Manduca sexta and Plutella xylostella. The genes encoding the class III GST of A. gambiae map to a region of the genome on chromosome 3R that contains a major DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] resistance gene, suggesting that this gene family is involved in GST-based resistance in this important malaria vector. In further support of their role in resistance, we show that the mRNA levels of aggst3-2 are approx. 5-fold higher in a DDT resistant strain than in the susceptible strain and demonstrate that recombinant AgGST3-2 has very high DDT dehydrochlorinase activity. (+info)
Cost-effectiveness and sustainability of lambdacyhalothrin-treated mosquito nets in comparison to DDT spraying for malaria control in western Thailand.
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The cost-effectiveness of lambdacyhalothrin-treated nets in comparison with conventional DDT spraying for malaria control among migrant populations was evaluated in a malaria hyperendemic area along the Thai-Myanmar border. Ten hamlets of 243 houses with 948 inhabitants were given only treated nets. Twelve hamlets of 294 houses and 1,315 population were in the DDT area, and another 6 hamlets with 171 houses and 695 inhabitants were in the non-DDT-treated area. The impregnated net program was most cost-effective (US$1.54 per 1 case of prevented malaria). Spraying with DDT was more cost-effective than malaria surveillance alone ($1.87 versus $2.50 per 1 case of prevented malaria). These data suggest that personal protection measures with insecticide-impregnated mosquito net are justified in their use to control malaria in highly malaria-endemic areas in western Thailand. (+info)
Impact of canine control on the epidemiology of canine and human visceral leishmaniasis in Brazil.
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Brazil is the only country endemic for zoonotic visceral leishmaniasis (ZVL) that regularly conducts epidemiologic and prophylactic control programs that involve the treatment of human cases, insect vector control, and the removal of seropositive infected dogs. This report reviews 60 studies reporting data on the efficacy of these recommended control tools and concludes that in Brazil 1) eradication of the disease in Minas Gerais was achieved by the concomitant use of the three control methods, 2) although seropositivity by an immunofluorescent assay is not completely related to infectiousness, the removal of seropositive dogs leads to a significant reduction of canine and human incidence, 3) improvement of the sensitivity of the diagnostic tool used for canine control should optimize the efficacy of control, and 4) although difficult and expensive, the public health dog control campaigns performed in Brazil reduced the incidence of ZVL and should be maintained since treatment of dogs is an unrealistic intervention, both because of its prohibitive cost and relatively poor effectiveness. (+info)
Reductive metabolism of p,p'-DDT and o,p'-DDT by rat liver cytochrome P450.
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The in vitro metabolism of p,p'-DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane], an important environmental pollutant, was examined in rat liver, focusing on reductive dechlorination. When p,p'-DDT was incubated with liver microsomes of rats in the presence of NADPH or NADH, a dechlorinated metabolite, p,p'-DDD [1,1-dichloro-2,2-bis(4-chlorophenyl)ethane], was formed under anaerobic conditions together with a dehydrochlorinated metabolite, p,p'-DDE [1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene]. p,p'-DDE was also formed from p,p'-DDD by liver microsomes. The dechlorinating activity was inhibited by carbon monoxide, metyrapone, and SKF 525-A (proadifen hydrochloride), but the dehydrochlorinating activity was unaffected. The reductase activity toward p,p'-DDT was induced by the pretreatment of rats with phenobarbital and dexamethasone. The dechlorination was catalyzed enzymatically by recombinant cytochrome P450 2B1, 3A1, 2B6, and 3A4. When p,p'-DDT was incubated with liver microsomes of rats in the presence of both a reduced pyridine nucleotide and FMN, p,p'-DDD was also formed under anaerobic conditions. In this case, the dechlorinating activity was not abolished when the microsomes were boiled. The reductase activities were inhibited by carbon monoxide. Hematin exhibited reductase activity toward p,p'-DDT in the presence of NADH and FMN. The activity of hematin was also supported by FMNH(2). The reductive dechlorination also seems to proceed nonenzymatically with the reduced flavin, catalyzed by the heme group of cytochrome P450. Similar enzymatic and nonenzymatic reducing activities were observed toward o,p'-DDT [1,1,1-trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane]. (+info)
Porphyria cutanea tarda: comparison of cases precipitated by alcohol and estrogens.
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A group of seven patients with porphyria cutanea tarda (PCT) precipitated by excessive alcohol consumption (A) was compared with a group of nine patients with PCT precipitated by estrogen therapy (B). Comparison was based on clinical signs, biochemical and morphologic evidence of liver disease, results of serum iron studies and response to therapy. Group A patients were men of mean age 57 years; group B patients were women of mean age 39 years who had been taking estrogen orally, either for contraception (in combination with progesterone) or as replacement therapy. Clinical signs were essentially the same in the two groups. Some patients in both groups had biochemical and morphologic evidence of liver disease. Group A patients had elevated values for serum iron and total iron-binding capacity, whereas patients in group B had normal or low values. Cessation of estrogen therapy of less than a year's duration brought about a spontaneous clinical and biochemical remission in group B patients. Otherwise, phlebotomy seemed to be the therapy of choice in both groups. (+info)
Dichlorodiphenyltrichloroethane (DDT): ubiquity, persistence, and risks.
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Due to uncontrolled use for several decades, dichlorodiphenyltrichloroethane (DDT), probably the best known and most useful insecticide in the world, has damaged wildlife and might have negative effects on human health. This review gives a brief history of the use of DDT in various countries and presents the results of epidemiologic and experimental studies of carcinogenesis. Even though its use has been prohibited in most countries for ecologic considerations, mainly because of its negative impact on wildlife, it is still used in some developing countries for essential public health purposes, and it is still produced for export in at least three countries. Due to its stability and its capacity to accumulate in adipose tissue, it is found in human tissues, and there is now not a single living organism on the planet that does not contain DDT. The possible contribution of DDT to increasing the risks for cancers at various sites and its possible role as an endocrine disruptor deserve further investigation. Although there is convincing experimental evidence for the carcinogenicity of DDT and of its main metabolites DDE and DDD, epidemiologic studies have provided contrasting or inconclusive, although prevailingly negative, results. The presence and persistence of DDT and its metabolites worldwide are still problems of great relevance to public health. Efficient pesticides that do not have the negative properties of DDT, together with the development of alternative methods to fight malaria, should be sought with the goal of completely banning DDT. (+info)
Food consumption and adipose tissue DDT levels in Mexican women.
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This article analyzes food consumption in relation to levels of DDE (the principal metabolite of DDT) in the adipose tissue of 207 Mexican women residing in States with high and low exposure to DDT. Data on the women's dietary habits and childbearing history were obtained from a personal interview. Adipose tissue DDE levels were measured by gas-liquid chromatography and compared by analysis of variance (ANOVA) and multiple linear regression. Adipose tissue DDE levels increased significantly with age (p = 0.005) and residence in coastal areas (p = 0.002) and non-significantly with the consumption of onion, cauliflower, prickly pear, squash blossoms, sweet corn, broad beans, chili pepper sauce, ham, and fish. Even so, during breastfeeding there was a non-significant reduction in these levels. The findings suggest that certain foods serve as vehicles for DDE residues and confirm that breastfeeding is a mechanism for the elimination of this insecticide, which accumulates over the years in the human body. (+info)