Chapters authored
Novel Approaches in Genetic Toxicology of Pesticides by Applying Fluorescent in Situ Hybridization Technique
Part of the book: Pesticides
Assessment of Potential Carcinogenicity by Quantitative Structure-Activity Relationship (QSAR)
Already in 1978, Elisabeth C. Miller and James A. Miller came with a presumption that electrophilic molecules are predicted to be carcinogens. It is because DNA molecule is reached in nucleophilic centres that may covalently bind to such substances. Rules deduced by Millers are even nowadays irrefutable, and they are used as the basis of testing of the substance for its carcinogenicity potential. Toxicological discipline that emerged from Millers’ research is based on dependence of chemical structure of the substance and their biological activity. Even further, there are strict regularities between molecular structures and activities. The tool used in assessment of biological activity of a substance is known as SAR, an abbreviation from structure–activity relationship. Besides electrophilic centres, in assessment of carcinogenic potential of a substance, the SAR also encounters chemical surrounding (neighbouring functional groups), size of the substance, its lipophilicity, number and position of aryl rings, substitutions of hydrogens, epoxides in aliphatic moieties or rings, resonance stabilisation, etc. To these days, SAR has been upgraded to quantitative SAR (QSAR) which applies multivariate statistical methods quantitatively comparing detected characteristics of “alerts” with biological activity of known carcinogens. Nowadays, chemical industry developing novel active substances is unthinkable without application of QSAR.
Part of the book: Genotoxicity
DNA Damage and Glutathione Peroxidase Activity in Liver and Kidney Cells in Wistar Rats Exposed to Terbuthylazine (TERB) for 28 Consecutive Days
The potential of low doses of the chloro-triazine herbicide terbuthylazine to induce DNA damage and impair activity of glutathione peroxidase (GPx) was evaluated in kidney and parenchymal and non-parenchymal liver cells of adult male rats. In a 28-day study, terbuthylazine was applied daily by oral gavage at doses: 0.004, 0.4 and 2.29 mg/kg bw/day. Tail Intensity (T Int) and Tail Length (TL) were used as descriptors of DNA damage. In the kidney, Tail Int was significantly different in all treated groups, while TL was different in 0.4 and 2.29 mg/kg bw/day groups, compared to controls. Significant differences in TL were recorded in parenchymal and non-parenchymal liver cells of all treated groups. Tail Int was significantly different from controls in non-parenchymal liver cells at all applied doses and in parenchymal cells at terbuthylazine doses of 0.004 and 2.29 mg/kg bw/day. A significant increase in GPx activity was observed only in the kidney at doses 0.4 and 2.29 mg/kg bw/day compared to the controls indicating its possible role in the protection of kidney from free radicals. It appears that repeated exposure to low doses of terbuthylazine could cause DNA instability in kidney cells and in parenchymal and non-parenchymal liver cells in rats.
Part of the book: Rodents