Evaluation of the genotoxic potential of cypermethrin, chlorpyrifos and their subsequent mixture, on cultured bovine lymphocytes.

Cypermethrin (CYP) and chlorpyrifos (CPF) are insecticides/parasiticides used in the production of fruits, vegetables and beef cattle. These substances or their metabolites are frequently reported as residues in food, whose consumption in a diet implies a genotoxic risk. The potential for chronic toxicity of CYP and CPF is unclear, and only a few genotoxicological evaluations based on their mixture have been performed. The aim of this study was to evaluate the genotoxic potential of CYP, CPF and CYP + CPF in five concentrations, from 5.9 to 175 µg/mL, on bovine lymphocytes. By means of the cytokinesis-block micronucleus cytome assay, a decrease in the cell proliferation index was observed (r = -0.89 p = 0.04); and also an increase in the frequencies of binucleated cells (BN) with micronuclei (BNMn) (r = 0.93, p = 0.02) and BN with nuclear buds (BNBud) (r = 0.778 p = 0.04), depending on the concentrations of CPF. An increase in BNMn frequencies was observed as a function of CYP concentrations (r = 0.89, p = 0.04) and also of the CYP + CPF mix (r = 0.99, p = 0.008). CYP caused greater genotoxic damage (BNMn) than CPF and the mixture on bovine lymphocytes. Cells with simultaneous presentation of micronuclei and nuclear buds were detected, as well as cells with irregular nuclei, something never previously reported, whose origin and significance should be investigated. The genotoxic effect of chlorpyrifos, cypermethrin and their mixture on bovine lymphocytes was observed. We recognized the value of the use of primary bovine cultures, animal species adjacent to man in the food chain, for genotoxicity studies.

Antioxidant capacity of vitamin C in mouse liver and kidney tissues

In the present study, the antioxidant capacity of vitamin C was examined in the liver and the kidney tissues of mice with or without ciprofloxacin (CFX) treatment. The antioxidant capacity of the vitamin was evaluated in terms of lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARs). The experimental design was 15 days of water (control and CFX groups) or vitamin C (vitamin C and vitamin C plus CFX groups) in drinking water. One dose of CFX was injected, 15 minutes before sacrifice, in the corresponding mice. The initial nmol of lipid hydroperoxides/g of tissue were 137 +/- 11 in the kidney and 145 +/- 15 in the liver, and the nmol of TBARs were 13 +/- 0.7 and 12 +/- 0.6, respectively.Pre-treatment with vitamin C reduced the levels of LOOH in the liver to 45 +/- 11 (p < 0.01) and vitamin C with CFX injection to 54 +/- 9 (p < 0.01). Vitamin C treatment also reduced the LOOH levels in the kidney roughly duplicated by CFX. Through the TBARs method we have not observed these effects. Quantification of LOOH is more sensitive than that of TBARs for estimating lipid peroxidation. CFX is used especially for urinary infections and can produce oxidative stress in the kidney. Pre-treatment with vitamin C may ameliorate this stress and also may improve the oxidative balance in the liver.(AU)

Antioxidant capacity of vitamin C in mouse liver and kidney tissues

In the present study, the antioxidant capacity of vitamin C was examined in the liver and the kidney tissues of mice with or without ciprofloxacin (CFX) treatment. The antioxidant capacity of the vitamin was evaluated in terms of lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARs). The experimental design was 15 days of water (control and CFX groups) or vitamin C (vitamin C and vitamin C plus CFX groups) in drinking water. One dose of CFX was injected, 15 minutes before sacrifice, in the corresponding mice. The initial nmol of lipid hydroperoxides/g of tissue were 137 +/- 11 in the kidney and 145 +/- 15 in the liver, and the nmol of TBARs were 13 +/- 0.7 and 12 +/- 0.6, respectively.Pre-treatment with vitamin C reduced the levels of LOOH in the liver to 45 +/- 11 (p < 0.01) and vitamin C with CFX injection to 54 +/- 9 (p < 0.01). Vitamin C treatment also reduced the LOOH levels in the kidney roughly duplicated by CFX. Through the TBARs method we have not observed these effects. Quantification of LOOH is more sensitive than that of TBARs for estimating lipid peroxidation. CFX is used especially for urinary infections and can produce oxidative stress in the kidney. Pre-treatment with vitamin C may ameliorate this stress and also may improve the oxidative balance in the liver.

Chromosomal damage in workers occupationally exposed to chronic low level ionizing radiation.

Chromosomal aberrations were evaluated in cultures of peripheral lymphocytes from subjects working in diagnostic X-ray and nuclear medicine areas, exposed to electromagnetic ionizing radiation and particulate ionizing emissions, respectively. A 4-fold increase in the level of chromosomal aberrations was found between the exposed and control groups without qualitative or quantitative cytogenetic differences between X-rays and nuclear medicine-exposed workers. Results are discussed in view of the early damage detection from chronic exposures particularly related to biological controls, hygienic improvements and overwork in a developing country.

Increased expression of 5q31 fragile site in a Bloom syndrome family.

In this work, we report spontaneous chromosomal breakpoints and fragile site expression induced by 5-fluorodeoxyuridine (FdUrd) and FdUrd plus caffeine in a family with Bloom's syndrome (BS) and 2 healthy donors. Standard and G-banded metaphases from each individual and each treatment were analyzed. Among the 59 common fragile sites (c-fra) identified in this work, only the frequency of 5q31 was significantly increased in the BS family with respect to healthy donors (P less than 0.005). A remarkable coincidence between the breakpoints involved in spontaneous chromosome aberrations and induced c-fra was found in BS homozygote patients. The importance of the interaction between fragile sites and chromosome rearrangements in cancer is discussed.

Lack of sensitivity of sister-chromatid exchange for lymphocyte chromosomal damage detection caused by antichagasic treatment.

No studies exist on sister-chromatid exchange (SCE) formation in chagasic patients therapeutically exposed to nifurtimox (NFX) or benznidazol (BZ). In the present study SCE was analyzed in cultures of peripheral lymphocytes of patients aged 11 months to 11 years treated with NFX 12-15 mg/kg/d for 60 days or with BZ 5 mg/kg/d for 30 days. Chagasic patients before treatment constituted a control group. A mean of 30 metaphases were examined for each individual. All treated patients compared with untreated controls did not show a significant increase in SCE frequency. Compared with the percentage of chromosomal aberrations in these patients and others belonging to the same epidemic protocol, SCE seems to be less sensitive in the detection of lymphocyte chromosomal damage caused by NFX or BZ.

[Bloom syndrome, constitutional and induced genetic instability in 2 cases from Argentina]. / Síndrome de Bloom, inestabilidad genética constitucional e inducida en dos casos de la Argentina.

Bloom's syndrome (BS) is a rare autosomal recessive hereditary disorder associated with pre- and postnatal growth deficiency, a characteristic facial configuration, an increased risk of chromosome instability, and an increased risk of neoplasia. BS is often lumped together with Fanconi's anaemia, ataxia telangiectasia and xeroderma pigmentosum, known as "chromosome instability syndromes". Since 1954, when Bloom's syndrome was defined, more then 100 cases have been diagnosed. The "Bloom's Syndrome International Registry" does not include any case detected in Argentina. Here, we report the cytogenetic study of a family affected by BS. Two siblings were studied. A 10-year-old boy named DaYu and a 17-year-old sister named CeYu. Both showed growth retardation from one month of age onwards, facial configuration characteristic, erythematous and sun-sensitive lesions of the skin of the face. To confirm the BS diagnosis of both, obtained from their clinical aspects, they were referred to our cytogenetic laboratory. Standard cultures of peripheral blood from DaYu and CeYu (homozygotes bl/bl) and their parents (heterozygotes bl/+) were performed for sister chromatid exchange (SCE) study. A group of 3 healthy donors (homozygotes +/+) was added for spontaneous and induced chromosomal aberration (CA) analysis. For the SCE study, bromodeoxyuridine was present in the cultures and slides were stained using the fluorescence plus Giemsa technique. For the analysis of induced CA, diepoxybutane (DEB) 0.1 microgram/mL was added 48 hours before harvesting. Both patients had a spontaneously increased rate of sister-chromatid exchanges (71.3 +/- 28.2 for DaYu and 76.9 +/- 37.9 for CeYu) similar to that found in Bloom's syndrome homozygotes.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirteenfold increase of chromosomal aberrations non-randomly distributed in chagasic children treated with nifurtimox.

Chromosomal aberrations were analyzed from cultures of peripheral lymphocytes in 2 groups of chagasic children, before and after treatment with nifurtimox. The mean incidence of chromosomal aberrations increased from control values of 1.75 +/- 1.39 (8 patients) to 23.55 +/- 9.55 (6 patients) at a significance of P less than 0.0001. G-banding analysis of chromosomal aberration sites revealed that treated patients present coincidence in the chromosome regions affected: 1p11, 1q11-12, 9q11-13, 17q11-21, 2p21, 2q23, 2q31, 2q33, 6p21, 6p21, 7q32, 13q14, 13q22, 15q22. These data indicate a non-random distribution of chromosomal aberrations induced by nifurtimox therapeutic treatment.

Assessment of cytogenetic damage in chagasic children treated with benznidazole.

Chromosomal aberrations and induction of micronuclei were analyzed from cultures of peripheral lymphocytes in 2 groups of chagasic children, before and after treatment with benznidazole. The median incidence of micronucleated interphase lymphocytes (20 patients) and chromosomal aberrations (10 patients) increased from control values of 5/1000 and 3% to 11.5/1000 and 6%, respectively, at a significance of P = 0.05.

Sister-chromatid exchange in spleenic lymphocytes of mice after exposure to nifurtimox or benznidazole.

The induction of sister-chromatid exchange (SCE) was analyzed in spleenic lymphocytes of mouse after exposure to nifurtimox (NFX) or benznidazole (BZ). Lymphocytes from Swiss mice treated "in vivo" with 1200 and 2000 mg/kg NFX (p.o.) and then incubated "in vitro" with bromo-2'-deoxyuridine showed an increased frequency of SCE. No significant differences were observed in mice treated with 2000 mg/kg BZ (p.o.). The present and previous results obtained in this and other laboratories suggest that the effects observed should warn against the potential risk of NFX treatment in humans receiving this chemotherapeutic agent as a treatment for Chagas' disease.

Micronucleus formation in bone marrow of mice treated with nifurtimox or benznidazole.

A single nifurtimox administration to male mice orally (p.o.) (600 - 2000 mg/kg) but not intraperitoneally (i.p.) was able to increase micronucleus formation in bone marrow significantly. No significant increase in micronucleus formation in the bone marrow of mice treated with benznidazole at dosages up to 2000 mg/kg, either p.o. or i.p., was observed. The potential mutagenic risk of nifurtimox treatment in patients suffering from Chagas' disease is analyzed.