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Comparative effects of structurally related cyclodiene pesticides on ATPases.

Comparative effects of aldrin, dieldrin, endrin, isodrin and telodrin, on different ATPase activities in beef heart mitochondrial and rat brain synaptosomal fractions were determined in vitro. Beef heart mitochondrial fractions were prepared by the conventional centrifugation method and the rat brain synaptosomes were prepared by Ficoll-sucrose gradient centrifugation method. Na+-K+-ATPase, oligomycin-sensitive and -insensitive Mg2+-ATPases, and K+-paranitrophenylphosphatase were determined in rat brain synaptosomes. In beef heart mitochondria, only the Mg2+-ATPase activities were determined. Concentration response curves were determined by assaying the enzyme activities in the absence and presence of 10-120 microM concentrations of each test chemical. Beef heart mitochondrial (oligomycin-sensitive) Mg2+-ATPase activity was inhibited by all five chemicals at all the concentrations tested. Aldrin and telodrin were the most potent inhibitors with an IC50 of 40 and 80 microM, respectively. About 30% was observed with dieldrin, endrin and isodrin, and the inhibition was not concentration-dependent. Oligomycin-insensitive Mg2+-ATPase was not significantly inhibited by any chemical except aldrin. Rat brain synaptosomal ATPases were also sensitive to these compounds. Aldrin and telodrin were more effective than other compounds. A 50% inhibition of oligomycin-sensitive Mg2+-ATPase activity was obtained at 80 microM of aldrin and telodrin. Na+-K+-ATPase and oligomycin-insensitive Mg2+-ATPase activities showed a maximum inhibition of 40% at the highest concentration tested for aldrin and telodrin. K+-paranitrophenylphosphatase was not inhibited significantly by any compound tested. These results suggest that ATPase system in rat heart and CNS may be selectively inhibited by aldrin and telodrin, but not by their structural analogs.

Adenosine Triphosphatases↗

Health risk assessment of residents living on harbour sludge.

A modelled approach for the assessment of exposure and health risks in a case of soil pollution with an unknown but probably large number of potential contaminants is presented. In 1983 the Steendijkpolder, a housing estate of about 800 houses, an agglomeration of schools and a tennis hall was built directly on a 4-m-thick layer of harbour sludge. The sludge originated from around 20 harbour basins in Rotterdam and the industrial area around the Nieuwe Waterweg. In the soil organic solvents, PAH's, aldrin, dieldrin, isodrin, telodrin and several heavy metals were found to be present as contaminants. Not all contaminants, including a number of halogenated compounds, were identified. The investigation of the other relevant environmental compartments in this situation, e.g. drinking-water, indoor-air and home grown vegetables showed that soil ingestion was the predominant route of intake of contaminants. Therefore the exposure of infants (age: 2-3 years) was calculated. The calculated intake of PAH by soil ingestion was around half the average intake of PAH in the daily diet. The extra exposure to drins (a group of cyclodiene insecticides) due to soil ingestion and inhaled contaminated indoor air was calculated to exceed twice the Acceptable Daily Intake (ADI) of dieldrin. The calculated maximal intake of Pb by soil ingestion exceeded the average intake of Pb in the daily diet by around 1.4 times. The maximal intake by soil ingestion of the other identified contaminants was relatively low. It was concluded that with the present knowledge the calculated exposure would not result in observable health damage.

Adult↗

Uptake and persistence of pesticides in cultured human cells.

The uptake and persistence of 14C-labeled pesticides in cultur-s of human embryonic lung diploid cells were studied. Chlordimeform, DDT, parathion, aldrin and dieldrin were selected as test compounds. Results obtained from these experiments divided the chemical into two groups. The first group consisted of three chemical DDT, aldrin and dieldrin which are generally classified as persistent insecticides while the second group was composed of chlordimeform and parathion, generally considered to be non-persistent insecticides. The rate of initial cellular incorporation of first group was approximately 20 to 70 times greater than the non-persistent insecticides. During the course of an incubation, the amounts of pesticide taken up by the cells decreased gradually.

Aldrin↗

Selection for insecticide resistance in the Australian sheep blowfly, Lucilia cuprina.

Egg implant studies on sheep demonstrate that the relative fitness of resistance genotypes of the sheep blowfly, Lucilia cuprina, changes over time for the 2 insecticides dieldrin and diazinon. The results suggest that selection may occur following exposure of larvae to sub-lethal concentrations and help to explain the relative rates of the development of resistance to dieldrin and diazinon by L.cuprina.

Animals↗

Evaluation of prenatal aldrin intoxication in rats.

The aim of the present study was to evaluate the impact of prenatal exposure to low doses of aldrin on physical and behavioral developments of rats (1-21 days old). To detect the possible persistent adversities produced by this exposure, the animals were also tested when adults (90 days old). Plasma determinations of both aldrin and its metabolite dieldrin and histopathological evaluations of brain slices were also performed in adult animals. Pregnant female rats were subcutaneously (s.c.) treated with aldrin (1.0 mg/kg) or with its vehicle (0.9% NaCl solution plus Tween-80) from day 1 of pregnancy until delivery. Results show that prenatal aldrin administration was able to decrease the median effective time (TE50) for incisor teeth eruption and to increase the TE50 for testes descent; other parameters indicative of physical development were not modified. Aldrin and dieldrin were not found in plasma of the adult rats; no differences were observed between control and experimental rats in the cellular and structural organization of the cerebral cortex neurones. Prenatal aldrin administration produced no impairment of adult animal's behavior in an avoidance learning test; nevertheless, the locomotor frequency of the experimental rats was higher than that of controls at 21 and 90 days old. When adults, these experimental rats had their performance in a hole-board apparatus (total number and duration of head-dips) also higher than that of the control ones. It was concluded that prenatal aldrin exposure induced not only developmental changes in the rat pups but also persistent behavioral alterations in adulthood, when the pesticide was not present in these animals.

Aldrin↗

Trends of chlorinated organic contaminants in great lakes trout and walleye from 1970 to 1998.

Levels of chlorinated organic contaminants in predator fish have been monitored annually in each of the Great Lakes since the 1970s. This article updates earlier reports with data from 1991 to 1998 for lake trout (Salvelinus namaycush) and (Lake Erie only) walleye (Sander vitreus) to provide a record that now extends nearly 30 years. Whole fish were analyzed for a number of industrial contaminants and pesticides, including polychlorinated biphenyls (PCBs), dichloro-diphenyl-trichloroethane (DDT), dieldrin, toxaphene, and mirex, and contaminant trends were quantified using multicompartment models. As in the past, fish from Lakes Michigan, Ontario, and Huron have the highest levels of PCBs, DDT, and dieldrin; Superior has the highest levels of toxaphene; and Ontario has the highest levels of mirex. In the period after curtailment of chemical use, concentrations rapidly decreased, represented by relatively short half-lives from approximately 1 to 9 years. Although trends depend on both the contaminant and the lake, in many cases the rate of decline has been decreasing, and concentrations are gradually approaching an irreducible concentration. For dioxin-like PCBs, levels have not been decreasing during the most recent 5-year period (1994 to 1998). In some cases, the year-to-year variation in contaminant levels is large, mainly because of food-web dynamics. Although this variation sometimes obscures long-term trends, the general pattern of a rapid decrease followed by slowing or leveling-off of the downward trend seems consistent across the Great Lakes, and future improvements of the magnitude seen in the 1970s and early 1980s likely will take much longer.

Animals↗

The hydration of sterically hindered epoxides by epoxide hydrolase of the rat and rabbit.

The hydration of the sterically-hindered epoxides dieldrin (HEOD) (1,2,3,4, 10,10-hexachloro-1,4,4a,5,6,7,8,8a-octahydro-6,7-epoxy-exo-1,4-endo-5,8- dimethanonaphthalene) and MME (1,2,3,4,9,9-hexachloro-1,4,4a,5,8,8a-hexahydro-6-methyl-6,7 epoxy 1,4-methanonaphthalene) was studied in pig and rabbit liver microsomes, and in apparently homogeneous preparations of epoxide hydrolase purified from liver microsomes of the rat and rabbit. A non-hindered substrate, HEOM (1,2,3,4,9,9-hexachloro-1,4,4a,5,6,7,8,8a-octahydro exo-6,7 epoxy-1,4 methano naphthalene) was used to assay both the enzyme preparations and the microsomes for epoxide hydrolase activity. The purified enzymes had more stable activity when incorporated into suspensions of phospholipid derived from rat liver microsomes than when used alone, so this preparation was used for long-term incubation with HEOD and MME. Activity towards the three substrates followed the sequence HEOM much greater than MME much much greater than HEOD, in the approximate ratios 1.5 X 10(6):10(4) activity towards dieldrin being only 0.0065-0.052 pmol/mg prot/min. The sole product of MME hydration was identified as a trans diol. The only product identified in the case of HEOD hydration by microsomes or enzyme preparations was the trans diol so there was no evidence for a significant metabolic pathway through the cis diol which is mediated by epoxide hydralase.

Animals↗

Rat liver cytochrome P-450 isozymes as catalysts of aldrin epoxidation in reconstituted monooxygenase systems and microsomes.

To explore which rat liver cytochrome P-450 species are involved in aldrin epoxidation, we have studied the catalytic activities of a series of cytochrome P-450 isozymes purified from untreated and inducer-treated Sprague-Dawley rats. Of ten cytochrome P-450 forms analyzed, seven isozymes, listed in order of decreasing activity, catalyzed aldrin epoxidation: P-450UT-A, P-450PB-C, P-450UT-H, P-450PB-B, P-450PCN-E, P-450UT-F, and P-450PB-D. P-450UT-I, P-450BNF-B, and P-450ISF-G were not very active at all. A novel aldrin metabolite, endo-dieldrin, was formed by cytochrome P-450UT-F in a 6-fold excess over dieldrin, which is the exo-isomer. The activity of aldrin epoxidase furthermore was assayed in liver microsomes from Sprague-Dawley rats of diverse physiological status and after pretreatment with various inducers resulting in a peculiar pattern of cytochrome P-450 isozymes. Untreated animals, at an age of 3 weeks, showed similar enzyme activities in both genders. During maturation, the activity of males increased by 3-fold, while the activity in females did not significantly change during this period. Pretreatment with pregnenolone-16-alpha-carbonitrile or dexamethasone strongly increased the activity in females. Pretreatment with dexamethasone did not increase the activity of males. A 50% depression of epoxidase activity was noted for males pretreated with 5,6-benzoflavone. Phenobarbital pretreatment increased the activity of females by 12-fold and of males by 2-fold. Males responded to pretreatment with polychlorinated biphenyls in a strain dependent fashion: enzyme activity was increased 2-fold in Sprague-Dawley rats but was not altered in Wistar rats. "Theoretical" values of microsomal epoxidase activity were calculated for weanling and adult Sprague-Dawley rats from turnover numbers and published data on the relative abundance of aldrin epoxidizing P-450 isozymes (Waxmann et al., Biochemistry 24, 4409, 1985). These values agreed with the activities determined. A similar statement can be made for male rats of both strains pretreated with inducers, when the ratio of enzyme activity of pretreated to control animals was used as a basis of comparison. The activity ratio of females pretreated with pregnenolone-16-alpha-carbonitrile, dexamethasone and phenobarbital, however, was much higher than the ratio calculated. Our results reveal that aldrin epoxidation is a reaction indicative of male specific and of phenobarbital-inducible cytochrome P-450 isozymes in rat liver.(ABSTRACT TRUNCATED AT 400 WORDS)

Aldrin↗

Application of the Tradescantia micronucleus assay for the genetic evaluation of chemical mixtures in soil and aqueous media.

Genotoxic evaluations of arsenic trioxide, dieldrin, lead tetraacetate and their nine binary and one tertiary mixtures were performed using the Tradescantia micronucleus (Trad-MN) assay. The chemicals or their mixtures were either (1) mixed into soil, and chemical exposure to the target cells was through the roots of intact plants grown in the soil or (2) through plant cuttings in which the inflorescences received treatment by absorption through stem of an aqueous solution of the test chemicals. All three chemicals yielded clastogenic responses when tested in soil medium and only two of these i.e. arsenic trioxide and dieldrin were positive when plant cuttings were exposed to the test chemicals in the aqueous medium. The clastogenicity of the chemical mixtures was modified by the ratio of the individual chemical in a particular mixture and also by the medium in which these mixtures were tested.

Arsenic↗

Combined effects of selected insecticides on humoral immune response in mice.

Biological effects data with single insecticides are far more abundant than with mixtures. These data cannot be used directly to predict the effects of insecticide mixtures. Three insecticides of different chemical classes: organochlorine; dieldrin, organophosphate; malathion, and carbamate; carbofuran, previously evaluated for their immunotoxic potential, were selected for studies of combined acute exposure in C57B1/6 inbred mice. The humoral response to sheep red blood cells (SRBC) and the functional activities of peritoneal macrophages, such as phagocytosis of fluorescent beads and presentation of a single protein antigen, avidin, were examined after in vivo exposure of mice to different combinations of the selected pesticides and compared with the vehicle controls. Regarding exposure to single substances, the data confirmed the immunosuppressive potential of dieldrin and carbofuran and the immunopotentiating effect of malathion. Following the acute concomitant exposure to dieldrin/carbofuran mixture, however, values for the parameters of antigen presentation, primary IgM antibody response to SRBC antigen, and macrophage phagocytosis, returned to control or above-control values, indicating a lack of any synergistic or additive effects of the chemicals on the immune response. Thus, it was concluded the dieldrin/carbofuran mixture had an antagonistic effect on the humoral response to SRBC and the macrophage phagocytic activity, in comparison with the action of administration of each of the insecticides alone.

Animals↗

Organochlorine and organophosphorous pesticide residues in ground water and surface waters of Kanpur, Uttar Pradesh, India.

A survey undertaken in Kanpur, northern India, has shown the presence of high concentrations of both organochlorine and organophosphorous pesticides in the surface and ground water samples. Liquid-liquid extraction followed by GC-ECD was used for the determination of these compounds. Among the various pesticides analyzed, high concentrations of gamma-HCH (0.259 microg/l) and malathion (2.618 microg/l) were detected in the surface water samples collected from the River Ganges in Kanpur. In the ground water samples collected from the various hand pumps located in agricultural and industrial areas, apart from gamma-HCH and malathion, dieldrin was also detected. The maximum concentration values of gamma-HCH, malathion and dieldrin were 0.900, 29.835 and 16.227 microg/l, respectively. Especially, the concentration of malathion was found to be much higher than the EC water quality standards in the ground water samples from industrial area posing a high risk to the common people. Pesticides like DDE, DDT, aldrin, ethion, methyl parathion and endosulfan were not detected in both the surface and ground water samples.

Agriculture↗

Spatial and temporal trends in surface water and sediment contamination in the Laurentian Great Lakes.

Data from recent sediment and surface water surveys have been collated and mapped to illustrate the spatial distribution of contaminants across the entire Great Lakes basin. Information from historical surveys, together with data from surface water monitoring programs in three major connecting channels, has also been collated in order to evaluate temporal trends. In general, Lakes Superior and Michigan exhibited the lowest levels of sediment contamination while Lake Ontario had the highest. Contaminants such as gamma-HCH (lindane) and dieldrin were ubiquitous in surface waters across the entire basin, which was indicative of atmospheric sources. The distribution of other compounds including hexachlorobenzene, octachlorostyrene and mirex indicated the presence of local sources within the watersheds of the connecting channels. Surficial sediment contamination was found to have decreased markedly since the late 1960s and 1970s. Similarly, surface water contamination decreased over the period 1986-1997 with concentrations of dieldrin, hexachlorobenzene, octachlorostyrene and mirex reduced by over 50%. However, the spatial distributions of both sediment and surface water contamination indicate that further effort is warranted in reducing local sources of contaminants, particularly in Lake Ontario.

Air Pollutants↗

Interaction of xenobiotics with estrogen receptors alpha and beta and a putative plasma sex hormone-binding globulin from channel catfish (Ictalurus punctatus).

Estrogens are important regulators of physiological functions. Although environmental contaminants (xenoestrogens) which interfere with estrogen signaling are of increasing concern, there is only limited information about their ability to interact with estrogen-binding proteins (SHBG) or receptors (ER). Recombinant ERalpha and beta were obtained after transient transfection of COS-7 cells with channel catfish ER cDNA. Plasma from adult female channel catfish was the source of SHBG. Tritiated estradiol (3H-E2) was used in standard radioligand-binding assays to characterize the binding properties of channel catfish SHBG (ccfSHBG) and to estimate the inhibition constants for various estrogenic compounds. Binding of 3H-E2 to ccfSHBG was saturable and of high affinity with a Kd (+/-SE) of 1.9+/-0.14 nM and a Bmax of 14.3+/-2.4 pmol/mg protein ( n = 3 assays). Additionally, ccfSHBG displayed binding specificity for androgens and estrogens. Endosulfan, 4-nonylphenol, and 4-octylphenol displaced 3H-E2 binding to ccfSHBG albeit only at very high concentrations, whereas dieldrin and atrazine showed little displacement activity even at the highest concentrations used. The synthetic estrogen ethynylestradiol had higher affinity than E2 for ccfSHBG. This finding differs from results with human and rainbow trout SHBG. The alkylphenolic compounds (4-octylphenol and 4-nonylphenol) displayed some ability to displace 3H-E2 binding from ERalpha and beta at high concentrations, but dieldrin and atrazine had little binding activity for both ER subtypes and endosulfan for ERbeta. The xenobiotics tested generally showed equivalent or greater affinity for ERalpha than ERbeta, whereas natural estrogens had much greater affinity for ERbeta than ERalpha. These observations suggest that results of studies using fish tissue ER extracts must be interpreted with caution, since both ER subtypes may be present, and that the binding of xenoestrogens to SHBG must be taken into account for proper assessment of endocrine disruption caused by environmental contaminants.

Animals↗

Incubation of superoxide dismutase with malondialdehyde and 4-hydroxy-2-nonenal forms new active isoforms and adducts. An evaluation of xenobiotics in fish.

The effects in fish (Sparus aurata) of dieldrin, previously reported to be an inducer of peroxisomal enzymes (Pedrajas et al., Comp. Biochem. Physiol. 115C (1996) 125-131), were compared with those of clofibrate. Although dieldrin provoked the more severe peroxisomal changes, both compounds induced oxidative stress as detected by the increased levels of microsomal thiobarbituric acid reactive substances; however the malondialdehyde (MDA) content, determined after HPLC separation of the MDA-TBA complex, was not significantly altered. These results suggest that, besides MDA, other aldehydes were formed in xenobiotic-injected fish, leading us to assess the oxidative effects of such xenobiotics by following changes in superoxide dismutase (SOD) pattern. New active SOD isoforms were detected by isoelectrofocusing in the light mitochondrial (LMF) and cytosolic (CF) fractions. Most of the new SOD bands could be reproduced in vitro by incubation of fish liver cell-free extracts with MDA. To clarify the effects of aldehydes, Cu,Zn- and Mn-SOD isoforms were purified and amino acid analysis was carried out. The new bands found in LMF and CF fractions were reproduced in vitro after incubation of pure SODs with MDA and 4-hydroxy-2-nonenal (HNE), the new SOD bands formed being coincident with the loss of Lys or His residues. Lysine residues were preferentially derivatized after treatment of Cu,Zn-SOD with MDA, but in Mn-SOD the lysine residues were modified only after treatment with MDA, while the histidine residues were modified only by HNE. No change of SOD activity was detected after MDA or HNE exposure, although at the higher aldehyde concentrations used protein aggregates were formed. Therefore, the appearance of new active SOD bands, after isoelectrofocusing separation, can be proposed as a biomarker of oxidative stress.

Aldehydes↗

Organochlorine exposure and risk of breast cancer.

BACKGROUND: Some organochlorine compounds may have weak oestrogenic effects and are, therefore, suspected of increasing the risk of breast cancer. We assessed prospectively the risk of breast cancer in relation to serum concentrations of several organochlorine compounds. METHODS: In 1976, serum samples from 7712 women were obtained from participants in the Copenhagen City Heart Study as part of physical examinations and interviews about lifestyle factors. During 17 years of follow-up, 268 women developed invasive breast cancer. Each woman with breast cancer was matched with two breast-cancer-free women from the remaining cohort. We analysed in 1996-97 the serum samples from 240 women with breast cancer and 477 controls. FINDINGS: Dieldrin was associated with a significantly increased dose-related risk of breast cancer (adjusted odds ratio 2.05 [95% CI 1.17-3.57], p for trend 0.01). Beta-hexachlorocyclohexane increased risk slightly but not significantly (p for trend 0.24). There was no overall association between risk of breast cancer and p,p'-dichlorodiphenyltrichloroethane or metabolites or for polychlorinated biphenyls. Exclusion of women with breast cancer diagnosed within 5 years of blood sampling strengthened the result for dieldrin, but did not affect the other results. INTERPRETATION: These findings support the hypothesis that exposure to xeno-oestrogens may increase the risk of breast cancer.

Adult↗

A biological loss of endosulfan and related chlorinated organic compounds from aqueous systems in the presence and absence of oxygen.

Endosulfan is a cyclodiene organochlorine currently widely used as an insecticide throughout the world. This study reports that the endosulfan isomers can be readily dissipated from aqueous systems at neutral pH in the absence of biological material or chemical catalysts, in the presence or absence of oxygen. The study showed that aldrin, dieldrin, and endosulfan exhibit bi-phasic loss from water in unsealed and butyl rubber sealed vessels. Half-lives are substantially increased for endosulfan I when oxygen is removed from the incubation vessel. The study conditions, where PTFE was used, were such that loss due to volatilization and alkaline chemical hydrolysis was eliminated. Half-lives determined from these data indicate that the parent isomers are much less persistent than the related cyclodienes, aldrin and dieldrin, confirming the findings of previous studies. The major oxidation product of endosulfans I and II, endosulfan sulfate, is less volatile and can persist longer than either of the parent isomers. Endosulfan sulfate was not formed in any of the treatments suggesting that it would not be formed in aerated waters in the absence of microbial activity or strong chemical oxidants. Since endosulfan sulfate is formed in many environments through biological oxidation, and is only slowly degraded (both chemically in sterile media and biologically), it represents a predominant residue of technical grade endosulfan, which finds its way into aerobic and anaerobic aquatic environments. The data obtained contributes to and confirms the existing body of half-life data on endosulfan I and II and its major oxidation product, endosulfan sulfate. The half-life data generated from the current study can be used in models for predicting the loss of chlorinated cyclodiene compounds from aqueous systems. The findings also highlight the importance of critically reviewing half-life data, to determine what the predominant processes are that are acting on the compounds under study.

Aerobiosis↗

The mammalian testis accumulates lower levels of organochlorine chemicals compared with other tissues.

Tissues were obtained from three separate experiments in order to quantify the tissue distribution of organochlorine chemicals that are thought to be potential reproductive toxicants in males: 1) Sprague Dawley rats received 1 microCi of 14C-Aldrin or 14C-Dieldrin (20.6 microCi/micromole) i.p. once a week for three weeks. One week and four weeks after the last injection, tissues were harvested and stored at -80 degrees C. Tissue 14C levels were quantified by scintillation spectrometry. 2) Cis- or trans-nonachlor (0, 0.25, 2.5, 25 mg/kg body weight) were administered daily in corn oil to male rats by gavage for 28 days. Tissues were harvested and frozen at -80 degrees C on the 29th day. Organochlorine residues were extracted and quantified by gas chromatography with electron capture detection. 3) Technical grade toxaphene (0, 0.1, 0.4 or 0.8 mg/kg body weight) was ingested daily by female cynomolgus monkeys of reproductive age for 18 months prior to being mated with control males. Dosing continued during pregnancy and lactation. Their infants received toxaphene via breast milk, and upon weaning, they ingested the same dose as their mothers for 48 to 49 weeks until, at 77 to 80 weeks of age, tissues were harvested and stored at -80 degrees C. Organochlorine residues were extracted and quantified as previously stated. In all three experiments, organochlorine residues in the testis were lower than in most of the other reproductive tract and nonreproductive tract tissues we examined. For example, testicular aldrin and dieldrin levels were <5% the epididymal content; testicular cis- and trans-nonachlor were <25% the epididymal content and, testicular toxaphene levels were <15% of the epididymal content. The reasons for the low degree of accumulation by the testis in comparison with other tissues are unknown. However, the lower testicular content may afford germ cells some protection from the potentially toxic effects of these chemicals.

Administration, Oral↗

The role of glutathion conjugation in the regulation of early toad embryos' tolerance to pesticides.

Reduced glutathion (GSH) content and glutathione S-transferase (GSH S-transferase) activity were investigated in developing toad embryos exposed to parathion, malathion, lindane and dieldrin. The embryonic GSH content was reduced after 96 h of incubation with 20.00 ppm malathion and 2.00 ppm lindane. Parathion and dieldrin did not produce any change. A similar effect was obtained in advanced stages of development (6-days larvae), but only with malathion. No correlation between the decrease in GSH level and mortality or morphologic abnormalities was observed. The four pesticides increased the activity of GSH S-transferase indicating that the enzyme is susceptible to induction during early development. The higher effect depicted by malathion may be related with an enhanced conjugation of the pesticide. Both GSH decrease and GSHS-transferase induction modifies the cell redox status and may indirectly influence transcription and translation. The early expression of GST genes provides the embryo with a useful mechanism for the regulation of tolerance against chemical stress.

Animals↗