Evaluation of the genotoxic, mutagenic, and histopathological hepatic effects of polyoxyethylene amine (POEA) and glyphosate on Dendropsophus minutus tadpoles.

Herbicides improve the productivity of a monoculture by eliminating weeds, although they may also be toxic and have negative effects on non-target organisms, such as amphibians. The present study evaluated the genotoxic, mutagenic, and histopathological hepatic responses of Dendropsophus minutus tadpoles to acute exposure (96 h) to the herbicide glyphosate (GLY, 65, 130, 260 and 520 µg/L) and the surfactant polyoxyethylene amine (POEA, 1.25, 2.5, 5 and 10 µg/L). On average, 174 % more genomic damage was observed in the tadpoles exposed to all concentrations of POEA in comparison with the control, while up to seven times more micronuclei were recorded, on average, at a concentration of 5 µg/L of POEA. All the individuals exposed to 10 µg/L of POEA died. The tadpoles exposed to GLY presented 165 % more DNA damage than the control, on average, at the highest concentrations (260 and 520 µg/L), and up to six times more micronuclei at 520 µg/L. The Erythrocyte Nuclear Abnormality test (ENA) detected a relatively high frequency of cells with lobed nuclei in the tadpoles expose to POEA at 5 µg/L and binucleated cells in those exposed to GLY at 520 µg/L. The hepatic histopathological observations revealed several types of lesions in the tadpoles exposed to both GLY and POEA. Overall, then, the results of the study indicate that both GLY and POEA have potential genotoxic, mutagenic, and hepatotoxic effects in D. minutus tadpoles. We emphasize the need for further studies to monitor the amphibian populations, such as those of D. minutus, which breed in aquatic environments associated with agricultural areas. The release of pollutants into natural habitats may have significant long-term impacts on the survival of anuran tadpoles.

Mutagenic, genotoxic and morphotoxic potential of different pesticides in the erythrocytes of Podocnemis expansa neonates.

Despite the damaging effects of pesticides glyphosate (Gly), atrazine (Atra) and fipronil (Fip) on different organisms, the mutagenic, genotoxic and morphotoxic potential of testudine erythrocytes in freshwater remains unknown. Thus, the aim of the present study is to assess the toxicological potential of these compounds in Podocnemis expansa (Amazonian turtles) neonates from eggs artificially incubated in substrate at different concentrations of herbicides Gly and Atra and insecticide Fip. Micronucleus test and other nuclear abnormalities, as well as comet assay and morphometric measurements taken of models' circulating erythrocytes were used as toxicity biomarkers. Pups exposed to Gly (groups Gly-65 ppb and Gly-6500 ppb) were the ones recording the largest amount of nuclear abnormalities; erythrocytes with multilobulated, notched and displaced nucleus were mostly frequent in groups Atra-2 ppb and Gly -65 ppb. All treatments (Gly-6500 ppb, Atra-2 ppb, Atra-200 ppb, Fip-4 ppb and Fip-400 ppb), except for group Gly-65 ppb, led to decreased erythrocyte area, increased "nuclear area: erythrocyte area" ratio, as well as to decreased erythrocyte and erythrocyte nuclei circularity, which highlights the clear effect on the size and shape of these cells. On the other hand, the comet assay did not evidence any genotoxic effect caused by the assessed pesticides. This is a pioneer study on the mutagenic and morphotoxic potential of pesticides in P. expansa eclodides exposed in ovo to Gly, Atra and Fip; therefore, it is an insight on how these compounds can affect the health of these animals.

Increased DNA damage is not associated to polymorphisms in OGGI DNA repair gene, CYP2E1 detoxification gene, and biochemical and hematological findings in soybeans farmers from Central Brazil.

Our study evaluated 163 individuals, being 74 soybean farmers, occupationally exposed to pesticides, and 89 individuals from Goias municipalities, Central Brazil, with similar conditions to the exposed group, comprising the control group. Of the 74 soybean farmers, 43 exposed directly to pesticides and 31 exposed indirectly. The exposed group consisted of individuals aged 19 to 63 years, 21 women and 53 men, and the control group had ages ranging from 18 to 64 years, being 36 women and 53 men. 18.9% of the exposed group were poisoned by pesticides, and the most common symptoms were headache and gastrointestinal problems. The genotype frequencies of the rs2031920 (T>C) polymorphism in the CYP2E1 gene present significant differences between the exposed and control groups (p = 0.02), showing that 24.3% of the exposed group were heterozygotes against 6.7% in the control group. For the OGG1 gene, two SNPs, rs1052133 (G>C) and rs293795 (T>C), were evaluated and the genotype frequencies were not statistically different between the exposed and control groups. The DNA damage was distinct (p < 0.05) in the three analyzed comet parameters (tail length, Olive tail moment, %DNA) between groups. However, there was no influence of age and alcohol consumption between the groups associated with the polymorphisms in the CYP2E1 and OGG1 genes and DNA damage. We also did not find altered hematological and biochemical parameters in the exposed group. Thus, this pioneering study at Goias State carried out an overview of the health of soybean farmers. We evaluated classic laboratory exams, associated with exposure markers (comet assay) and susceptibility markers (genetic polymorphisms), emphasizing the need to expand the Brazilian health assessment protocol. We found, in soybean farmers, increased DNA damage and a higher number of heterozygotes in CYP2E1 gene, compared with the control group, despite the lack of association with age, educational level, smoking, drinking habits, and genetic polymorphisms.

DNA damage in peripheral blood lymphocytes and association with polymorphisms in the promoter region of the CYP2E1 gene in alcoholics from Central Brazil.

DNA damage caused by the accumulation of bio-products generated in the biotransformation of ethanol to acetaldehyde mediated by the CYP2E1 enzyme has been studied. To evaluate DNA damage in peripheral blood lymphocytes and the possible association with polymorphisms in the promoter region of the CYP2E1 gene, we performed a case-control study including 75 alcoholics and 59 individuals who consume alcohol socially. Alcoholics were previously diagnosed by the Psychosocial Care Center - Alcohol and Drugs (CAPS A/D) in the city of Goiania, Goias state, Central Brazil. DNA damage was evaluated by comet assay. The analysis of the rs3813867, rs2031920, and rs2031921 polymorphisms in the promoter region of CYP2E1 gene was performed by Sanger sequencing. Men older than 35 years old were the most common alcoholics. We found increased DNA damage in the case group, compared to the control group (p < 0.001). Alcoholics who were heterozygous in the rs3813867, rs2031920, and rs2031921 polymorphisms showed higher DNA damage (tail length and olive tail moment), compared to individuals with the homozygous non-mutated allele. Previous studies have shown that polymorphisms in the promoter region of the CYP2E1 gene could cause higher CYP2E1 transcriptional activity, increasing enzyme activity compared with nondrinkers, indicating that the presence of the mutated allele (heterozygous or homozygous) may be associated with higher alcohol metabolic rates and therefore show increased acetaldehyde levels after alcohol consumption, which then can exert its carcinogenic effect.

Genotoxic and Cytotoxic Effects of Antiretroviral Combinations in Mice Bone Marrow.

Commonly used guidelines for the management of human immunodeficiency virus (HIV) infection (highly active antiretroviral therapy, HAART) include drug combinations such as tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) and combivir [zidovudine (AZT) + 3TC] + efavirenz (EFV). These combinations may enhance the genotoxic effects induced by such drugs individually, since the therapy requires lifelong adherence and the drugs have unknown effects during treatment. Thus, the evaluation of the benefits and risks of HAART is of great importance. In order to assess the cytotoxic and genotoxic potential of three concentrations of each of the antiretroviral combinations TDF + 3TC (800 + 400, 1600 + 800, and 3200 + 1600 mg/kg body weight, BW) and combivir + EFV (200 + 100 + 400, 400 + 200 + 800, and 800 + 400 + 1600 mg/kg BW) after two exposure periods (24 h and 48 h), in the present study the in vivo comet assay (single-cell gel electrophoresis) and the mouse bone marrow micronucleus test were used. Neither TDF + 3TC nor combivir + EFV induced DNA damage at any concentrations tested after 24 h or 48 h using the comet assay. After 24 h, both combinations increased the micronucleus frequency at all concentrations tested. After 48 h, combivir + EFV increased the micronucleated polychromatic erythrocyte (MNPCE) frequency at the two highest concentrations tested. Polychromatic erythrocytes (PCE)/normochromatic erythrocytes (NCE) ratio was high for both combinations, suggesting that they can be mitogenic. Since genotoxicity may be related to carcinogenesis, it is necessary to conduct further studies to verify the long-term mutagenic effects of these drugs.