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Suppression of testicular steroidogenesis in rats by the organochlorine insecticide Aldrin.

Treatment with Aldrin, an organochlorine insecticide, for 13 and 26 days caused suppression of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activities, along with accumulation of cholesterol in the testicular tissues of adult rats. The same treatment also resulted in a reduction in the nuclear diameter of Leydig cells (LCND) and diameter of seminiferous tubules. A decrease in the weight of testes, seminal vesicles and ventral prostate was also noted. HCG administration in the long-term (26 days) treatment restored the steroidogenic enzymes activity and the nuclear diameter of the Leydig cells. It also reduced the accumulation of tissue cholesterol towards the vehicle-injected controls. The inhibition of steroidogenesis in the testes possibly reflects a decrease in pituitary gonadotrophin release after the treatment with Aldrin.

Journal Article↗

Induction of DNA damage by N-nitrosodiethylamine in rat hepatoma cells: correlation with cytochrome P450-mediated aldrin epoxidase activity.

The genotoxic potency of the hepatocarcinogen N-nitrosodiethylamine (NDEA) was tested in various Reuber hepatoma cell lines, which differ in their expression of differentiated liver specific functions including hepatic cytochrome P450 forms, and in rat hepatocytes, with the aim of characterizing the enzymes involved in activation. DNA single-strand breaks assessed by alkaline elution served as an indicator of genetic damage. Aldrin epoxidase activity was used as a marker for various hepatic cytochrome P450 forms. The poorly differentiated cell lines RH35 and H4IIEC3/T were apparently not affected by NDEA; moderate effects were observed in the well-differentiated lines H4IIEC3/G- and 2sFou, and major effects in two other well-differentiated lines, Fao and C2Rev7, and in hepatocytes. The degree of DNA damage in the cell lines correlated positively with the expression of aldrin epoxidase. Furthermore, DNA damage induced by N-nitrosodimethylamine (NDMA) was determined in C2Rev7 cells and in rat hepatocytes in order to assess a possible involvement of the NDMA-metabolizing cytochrome P45oIIE1 in the activation of NDEA by comparing the genotoxic potencies of the two compounds. NDMA was distinctly less effective than NDEA in C2Rev7 cells at all concentrations tested. In hepatocytes, NDMA induced more DNA damage than NDEA at low concentrations, but was slightly less active at high concentrations. The results suggest that NDEA is preferentially metabolized to genotoxic products by one or several cytochrome P450 forms different from P450IIE1.

Animals↗

Degradation of endrin, aldrin, and DDT by soil microorganisms.

Twenty microbial cultures which had been shown to degrade dieldrin were tested to determine their ability to degrade endrin, aldrin, DDT, gamma isomers of benzenehexachloride (gamma-BHC), and Baygon. All isolates were able to degrade DDT and endrin, whereas 13 degraded aldrin. However, none of them was able to degrade Baygon or gamma-BHC.

Arthrobacter↗

In vitro studies on the metabolism of aflatoxin B1 and aldrin in testes of genetically different strains of Drosophila melanogaster.

As Drosophila melanogaster occupies an important position within the test battery for mutagens and carcinogens, it is of interest to study the xenobiotics metabolism of this insect. Likewise, the genetic control of these important enzyme systems falls within this interest. Our attempt was to get new strains, which show changes in their xenobiotics metabolism. This was done by a mutagenization and selection procedure for the second chromosome. The 44 fertile homozygous inbred strains produced by this selection were first tested for DDT resistance. Some of them showed LT50 values which were remarkably higher than that of the original strain Berlin K. Aflatoxin B1 metabolism in two of the new strains (H349 and H362), Berlin K, and Hikone-R was compared, whilst aldrin epoxidase activity was compared in strains H349, H362, Berlin K, vestigial, and Karsnäs-R. The metabolism studies were carried out in vitro with testes tissue of the different strains. The metabolism in testes is of specific interest because this tissue is most often used in mutagenicity testing. In the AFB1 assays of the up to 12 observed metabolites three could be identified as AFB2a, AFM1, and AFR0. Hikone-R produced mostly AFR0 (3.43% of the initial AFB1 concentration) and small amounts of AFM1 (0.59% AF and AFB2a (0.36% AF). The strain Berlin K showed only a low production of AFB2a (0.48% AF), while the strain H349 formed AFR0 (6.02% AF) and AFM1 (0.75% AF). The AFM1 appeared in even higher amounts than with Hikone-R. On the other hand, H362 showed the lowest activity in AFB1 metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxin B1↗

Dieldrin and DDT in the tissues of mice fed aldrin and DDT for seven generations.

Seven-Generation Study (P-F6): The concentration and total retention of dieldrin or p,p'-DDT and metabolites were determined in the total carcass of Swiss-Webster mice fed dietary supplements of aldrin 5 or 10 ppm, or DDT 100 ppm, to age 260 days. All groups showed a significant increase in total body retention (and concentration) of dieldrin or total DDT in the total carcass of the F1, F2, and F3 generations. Generally, these increases were related directly to increases in total body lipids, when compared with the P generations. The control (pesticide-free) diet was fed to all F4 generation experimental mice from weaning to age 260. The pesticides absorbed by these animals while in utero and via lactation were found, at the time of sacrifice, to have been excreted completely. When the experimental diets were resumed with the weanlings of the F2 generations, a repetition of the general findings in the P and F1 generations was noted-demonstrating that pesticide retention and total body lipids are closely interrelated, and that a high body lipid content favors a high retention rate of these fat-soluble pesticides. These results support our earlier studies in rats (Deichmann et al., 1972) and investigations with cirrhotic human livers with severe fatty infiltration (Oloffs et al., 1974). Conception became more delayed with each succeeding generation, requiring some degree of "selective" breeding of the F4, F5, and F6 generations.

Adipose Tissue↗

Selective binding of aldrin and dieldrin in cartilage.

Whole body autoradiography of 14C-aldrin and 14C-dieldrin in pregnant mice indicated a slow but persistent uptake of both substances in cartilage, e.g. in the vertebral and epiphyseal discs. Also in the fetal skeleton a marked accumulation was observed.

Aldrin↗

A toxic reagent-free method for normal-phase matrix solid-phase dispersion extraction and reversed-phase liquid chromatographic determination of aldrin, dieldrin, and DDTs in animal fats.

A method for the determination of aldrin, dieldrin, DDT, DDE, and DDD contamination in animal fats (beef tallow, lard, and chicken fat) without using toxic reagents is developed, that uses high-performance liquid chromatography after the sample has been prepared by matrix solid-phase dispersion (MSPD) with acidic alumina oxide. A reversed-phase C(1)-silica column with a mobile phase of 50% (v/v) ethanol solution (in water) and a photo-diode array detector were used for the determination. Average recoveries of the target compounds (0.2-5.0 microg g(-1)) ranged from 84-98%, with coefficients of variation of <5%. The limits of quantitation were </=0.16 microg g(-1 )for AD, </=0.10 microg g(-1) for DD, </=0.06 microg g(-1) for DDT, </=0.07 microg g(-1) for DDE, and </=0.05 microg g(-1 )for DDD. No toxic reagents were used at all.

Aldrin↗

Aldrin epoxidase and dimethylhydrazine demethylase activities in tumorous and non-tumorous tissue of the human colon and rectum.

High activities of aldrin epoxidase and dimethylhydrazine demethylase were found in human colon and rectum mucosa, the first being as high as in human liver biopsy specimens. Comparisons between tumorous (adenocarcinomas) and non-tumorous tissues of the same individuals revealed loss of activities in tumorous specimens. The presence of epoxidizing enzymes and demethylation of the organ-specific colon carcinogen dimethylhydrazine (DMH) in the intestinal muscosa of tumor-bearing patients implicate them with chemical carcinogenesis also in humans.

Adenocarcinoma↗

Effect of intratracheally administered lindane on aldrin and benzo(a)pyrene contents in lungs of rats.

Pretreatment with lindane resulted in inhibition of benzo(a)pyrene hydroxylase activity in the lungs of rats. The enzyme activity tended to return to normal 5 days after the administration of lindane. Studies with benzo(a)pyrene and aldrin indicated reduced elimination of these compounds from the lungs of lindane-treated animals, suggesting that lindane may alter the clearance of certain substances or compounds from lungs. The delayed clearance of these compounds from lungs may be an indirect effect of lindane related to inhibition of certain metabolizing enzymes.

Aldrin↗

Distribution of aldrin and its epoxide (dieldrin) in egg-forming tissues and eggs of laying hens following an oral application.

Laying hens were treated orally with a single dose of aldrin (1,2,3,4,10,10-hexachloro-1,4,4a,5,8,8a-hexahydro-1,4:5,8-dimethanonaphthalene, AD) 1 mg kg(-1) bw. Concentrations (microg g(-1)) of AD or its epoxide, dieldrin (1,2,3,4,10,10-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydroendo-,exo-1,4:5,8-dimetha-nonaphthalene, DD), in the main tissues involved in egg formation (blood, liver, ovary, and oviducts) and egg yolk, collected at 1 day after AD dosing, were determined by normal-phase high-performance liquid chromatography. The limits of determination were 0.07 microg g(-1) for AD and 0.08 microg g(-1) for DD, respectively. In extractable fats from the above tissues and egg yolk, AD was found in the egg yolk; however, no AD was found in tissues involved in egg formation. DD was found in all tissues examined here. The DD level was highest in the liver and was lowest in the blood (P<0.01). These results suggest that the epoxidation of AD to DD occurred rapidly in the hen.

Administration, Oral↗

Age-related changes in O-deethylase and aldrin epoxidase activity in mouse skin and liver microsomes.

The metabolism of three model substrates for the cytochrome P450 dependent mono-oxygenase enzyme system (P450-MMO) was studied in microsomes isolated from skin and liver of young adult and senescent C57B1/6J mice. The substrates chosen were aldrin (AE), 7-ethoxycoumarin (EOC), and 7-ethoxyresorufin (EOR). Both EOC and EOR activities were lower in senescent skin. By contrast, no-age related changes were seen in senescent liver. AE was similar in young and old, in both tissues. We suggest that some important age-related differences in cutaneous xenobiotic metabolism do occur, but that these are not mirrored by hepatic differences, and are substrate specific. Previous work from these laboratories would also suggest significant species differences.

Aging↗

Normal-phase high-performance liquid chromatographic determination and identification of aldrin, dieldrin, and DDTs in eggs.

A method for the routine monitoring of residual aldrin, dieldrin, pp'-DDT, op'-DDT, pp'-DDE, and pp'-DDD in eggs by high-performance liquid chromatography (HPLC) with a photo-diode array (PDA) detector is described. The lipids extracted from a whole egg are cleaned by a solid-phase extraction (SPE) ISOLUTE NH2 column with a diethyl ether-hexane (5:95, v/v) eluent. The HPLC separation is carried out using a normal-phase (LiChrosorb NH2) column, a heptane-hexane eluent (97:3, v/v), and a PDA detector. The average recoveries from fortified target compounds (0.1, 0.2, 0.3, and 0.4 microg/g, respectively) are > or = 83%, with standard deviations (SDs) between 2 and 5%. The interassay variabilities and their SDs are < or = 4.8% and < or =0.7%, with intra-assay variabilities of 2.1-3.3%. The limits of determination for these compounds range from 0.04 to 0.08 microg/g.

Aldrin↗

Epoxidation of aldrin to exo-dieldrin by soil bacteria.

Twenty-two strains of soil bacteria, including representatives of the genera Bacillus, Micromonospora, Mycobacterium, Nocardia, Streptomyces, Thermoactinomyces, and Pseudomonas and 10 unidentified gram-negative, motile, rod-shaped bacteria, were shown to degrade aldrin to its epoxide dieldrin. In every case, the exo-stereoisomer of dieldrin was produced exclusively.

Aldrin↗

Histopathology of carcinomas of the liver in mice ingesting dieldrin or aldrin.

C3HeB/Fe male and female mice, ingesting 10 ppm of the pesticides dieldrin or aldrin in the diet, developed highly significant incidences of carcinomas of the liver. The carcinomas varied from well differentiated to poorly differentiated and undifferentiated and were capable of metastasis.

Adenoma, Bile Duct↗

In vitro hepatic biotransformation of aldrin and dieldrin in food-producing animals.

The hepatic biotransformation of aldrin (AD) and dieldrin (DD) was studied in liver post-mitochondrial supernatants (S-9s) from laying hens, female cattle and swine. S-9s were incubated with 0.03 nmol of AD or DD for 1 h. After 1 h, AD in the samples was almost epoxidated to DD. This formation was found with all the animal S-9s, and the highest rates occurred in pig S-9 (P < 0.01), followed by cow and hen S-9s. No reduction of DD was found with any of the S-9s.

Aldrin↗

Decreasing half-life of dieldrin in egg yolk following a single oral administration of aldrin to laying hens.

Laying hens were treated orally with a single dose of aldrin (AD) 1 mg/kg body weight. Concentrations (microgram/g) of AD or its epoxide (= dieldrin, DD) in the yolk of eggs laid for 21 days after AD treatment were determined by normal-phase high-performance liquid chromatography. The limits of determination were 0.02 microgram/g for AD and 0.03 microgram/g for DD, respectively. After AD treatment, although the low levels of AD (mean 0.02-0.03 microgram/g) were observed only during a three-day period (from 4th to 6th days), DD (mean 0.15 microgram/g) was found already on the 2nd day, indicating that the epoxidation of AD to DD in the hen's body is rapid. The highest level of DD (mean 0.40 microgram/g) was detected on the 6th day, and then DD levels decreased slowly and were detected up to the 21st day. In this decreasing phase, the half-life of DD in the yolk was estimated to be 25.6 days with a 95% confidence interval from 22.7 to 29.4 days.

Administration, Oral↗

Rapid method for extracting aldrin, dieldrin, and endrin from visceral material.

A simple method is described for purifying aldrin, dieldrin, and endrin from visceral material by using a Celite column. Celite retains all interfering materials including Lipids whereas the chlorinated Insecticides are eluted from the column with n-hexane. This extract can be used directly for gas chromatographic analysis.

Adsorption↗

Aldrin and lindane impact on acid and alkaline phosphatase activities of prawn, Metapenaeus monoceros: in vitro study.

Activity levels of acid and alkaline phosphatases in hepatopancreas, stomach, muscle, gill and brain tissues of penaeid prawn, Metapenaeus monoceros were studied after in vitro addition of different concentrations of aldrin and lindane, the organochlorine insecticides. The activity levels of both these enzymes were inhibited significantly in all the tissues of prawn and the degree of inhibition is increased with increase in the concentration of insecticide. The significant inhibition creates disturbances in the normal functioning such as disturbances in the normal functioning such as disturbances in protein synthesis and different biochemical lesions in selected tissues of prawn, M. monoceros.

Acid Phosphatase↗