The effect of acute dichlorodiphenyltrichloroethane exposure on hypermethylation status and down-regulation of p53 and p16INK4a genes in rat liver.

The aim of the study was to investigate the early effect of acute dichlorodiphenyltrichloroethane (DDT) exposure on the methylation status of the promoter region of two tumor suppressor genes: p53 and p16(INK4a) (p16) in rat liver. We analyzed their transcript and protein expression profiles concurrently with the examination of transcriptional and protein expression levels of DNA (cytosine-5)-methyltransferase 1 (Dnmt1). Male Wistar rats were treated with a single dose of DDT (57 mg kg(-1) of body weight) and the methylation status of p53 and p16 genes was examined after 24 h using methylation-sensitive restriction analysis-MSRA.

The effect of phenobarbital on gene expression levels of p53 and Dnmt1 in the liver of Wistar rats.

Background: Our previous studies have shown that short-term treatment with phenobarbital (PB) resulted in cytosine methylation of CpG sites on the p53 gene promoter in male Wistar rats' liver. Furthermore, PB induced DNA-methyltransferases (DNMTs) activity was also demonstrated; being the enzymes that catalyze methyl group transfer to cytosine in CpG dinucleotides.

Objective: Since DNA methylation is involved in regulating gene transcription and that DNMT1 is implicated in regulating DNA methylation, this study assessed whether PB-induced hypermethylation of the p53 promoter region was associated with an altered expression of p53 and Dnmt1 genes.

Changes of c-Myc and DNMT1 mRNA and protein levels in the rat livers induced by dibutyl phthalate treatment.

We investigated the relationship between dibutyl phthalate (DBP)-induced hypomethylation of the c-Myc promoter region (as evident in our early study) and the expression of c-Myc and DNMT1 genes (at messenger RNA (mRNA) and protein level) in the rat liver. Male Wistar rats received DBP in 1, 3, or 14 daily doses of 1800 mg kg(-1) body weight. Levels of DNMT1, c-Myc mRNA, and proteins were detected using real-time polymerase chain reaction and Western blot analysis, respectively.

[The effect of dibutyl phthalate (DBP) on the methylation and expression level of p53 gene in the liver of Wistar rats].

Background: Currently, nongenotoxic carcinogens-induced changes in DNA methylation profile are considered as mechanism of their toxicity, including carcinogenic action.

Objective: The aim of the study was to determine the effect of dibutyl phthalate (DBP) on the methylation levels of the p53 promoter region, as well as mRNA and protein level of this gene.

Material And Method: Male Wistar rats received DBP in one, three or fourteen daily oral doses (at 24-h intervals) of 1800 mg/kg b.

[Cumulative exposure to pesticide residues in food].

The results of food monitoring studies indicate that humans are constantly exposed to residues ofplant protection products (pesticides) in marketed food products. Hence, assessment of the risk to consumers associated with the consumption of products containing residues of the active substances of pesticides is a key stage in both the registration of pesticides and official control of foodstuffs. However there are frequent cases of exposure not only to individual active substances but also to mixtures of pesticide residues.

[Toxicogenomics in hazard assessment of chemicals].

Recent changes in the European legislation of chemicals suggest an urgent need for introduction of novel, alternative methods for testing chemical substances. Such possibility is offered by toxicogenomics--a scientific discipline combining knowledge from the field of toxicology, i.e.

Di-butyl phthalate-induced hypomethylation of the c-myc gene in rat liver.

Peroxisome proliferators (PPs)-induced DNA hypomethylation has been proposed as a mechanism of their toxicity, including carcinogenic action. The effect of di-butyl phthalate (DBP), a known peroxisome proliferators, on the methylation level of the c-myc promoter region in rat liver was studied. Changes in the methylation status of the c-myc gene were correlated with changes in DNA synthesis, DNA methyltransferase (DNMTs) activity and liver weight.

[Phenobarbital-induced hypermethylation of the p53 promoter region in the liver of Wistar rats].

Non-genotoxic carcinogens (NGCs)-induced changes of DNA methylation has been proposed as a mechanism of their toxicity, including carcinogenic action. The effect of phenobarbital (PB), a rodent liver carcinogen on the methylation level of the p53 promoter region in rat liver was studied. Changes in the methylation status of the p53 gene were correlated with changes in DNA synthesis, DNA methyltransferase (DNMTs) activity and liver weight.

[Violations of mrls for pesticide residues in food reported for risk assessment according to RASFF procedures in Poland].

The results of risk assessment to evaluate the potential risk from food products of plant origin in cases of violations of maximum residue limits for pesticides (MRLs) have been presented. According to the rules set in the RASFF any violation of legally established limit should undergo the risk assessment to allow quantitative approach in hazard evaluation for consumers. The basis of risk assessment have been presented as tool for risk management in the official food control.

The effect of phenobarbital on the methylation level of the p16 promoter region in rat liver.

It has been suggested that non-genotoxic carcinogens (NGCs) may cause modification of the DNA methylation status. We studied the effects of phenobarbital (PB) -- a non-genotoxic rodent liver carcinogen -- on the methylation level of the promoter region of the p16 suppressor gene, as well as on hepatomegaly, DNA synthesis, and DNA-methyltransferase (DNMTs) activity in the rat liver. Male Wistar rats received PB in 1, 3 or 14 daily oral doses (at 24-h intervals), each equivalent to 1/10 of the LD(50) value.

[DNA methylation--alternative mechanism of chemical carcinogenesis].

It is increasingly accepted that the initiation of chemical carcinogenesis should be considered as a transformation process of a normal cell caused by genetic changes, i.e. mutational DNA damage and/or epigenetic changes, which render normal gene expression impossible with the preservation of the DNA sequence intact.

[The role of nuclear receptors in cytochrome P-450 induction by xenochemicals].

This review summarizes recent findings indicating that members of the orphan nuclear receptor superfamily regulate the synthesis of their CYP genes which code CYP enzymes involved in metabolism of endogenous and exogenous compounds. The foreign compounds metabolism and the role played by individual cytochrome P450 (CYP) enzymes in the activation and detoxification of xenochemicals prevalent in the environment are important areas of molecular pharmacology and toxicology. The advances in our understanding of the mechanisms through which foreign chemicals impact on these CYP-dependent metabolic processes have been made during the past years.

Hepatocellular peroxisome proliferation and DNA synthesis in Wistar rats treated with herbicide fluazifop.

The aim of this study was to determine the effect of herbicide fluazifop, on the early occurring changes in rat liver regarded as hepatic markers of peroxisome proliferators (PPs). Fluazifop was administered orally to male Wistar rats at increasing doses from 5.6 to 891 mg/kg body weight per day for 1, 2, 4, 7 and 14 consecutive days and peroxisome proliferation, induction of some peroxisome-associated enzymes and mitogenesis (S-phase, M-phase and percentage of binucleated hepatocytes) were studied.

[Effect of diclofop on the activity of some drug-metabolizing enzymes in the liver of male Wistar rats].

The study was designed to determine whether diclofop, introduced to environment as herbicide, would exert properties of chemical inducers of rat liver monooxygenase system related to CYP1A and CYP2B isozymes. For this purpose, the effect of diclofop on 7-etoxyresorufin O-dealkylase and p-nitroanisole O-demethylase activities specific for CYP1A as well as on CYP2B mediated 7-pentoxyresorufin O-dealkylase activity was studied in male Wistar rats. This biochemical method permits to determine whether tested compound belongs to one of two main types of chemical inducers.