ABSTRACT
The genotoxic effects of methyl bromide were investigated in a DNA-binding study. [14C]Methyl bromide was administered to male and female F-344 rats orally, or by inhalation from a closed exposure system. DNA adducts were detected in the liver, lung, stomach and forestomach. [14C]3-Methyladenine, [14C]7-methylguanine and [14C]O6-methylguanine were identified using a combination of three different methods of hydrolysing DNA, followed by HPLC or gas chromatography-mass spectrometry. After both oral and inhalation exposure, the highest levels of methylated guanines, especially those of [14C]O6-methylguanine, were found in the stomach and forestomach of the rats. These results clearly demonstrate a systemic DNA-alkylating potential of methyl bromide.
Subject(s)
DNA/metabolism , Guanine/analogs & derivatives , Hydrocarbons, Brominated/toxicity , Liver/drug effects , Lung/drug effects , Stomach/drug effects , Administration, Inhalation , Administration, Oral , Animals , Carbon Radioisotopes , Chromatography, High Pressure Liquid , DNA/analysis , Female , Gas Chromatography-Mass Spectrometry , Gastric Mucosa/metabolism , Guanine/analysis , Hydrocarbons, Brominated/administration & dosage , Liver/metabolism , Lung/metabolism , Male , Rats , Rats, Inbred F344 , Sex FactorsABSTRACT
The genotoxic potency of methyl iodide was investigated in a DNA binding study. Male and female F344 rats were exposed to 14C-labelled methyl iodide orally or by inhalation in a closed exposure system. DNA adducts were detected in the liver, lung, stomach and forestomach of the exposed animals. [14C]3-Methyladenine, [14C]7-methylguanine and [14C]O6-methylguanine could be identified by a combination of three different methods of hydrolysing DNA and subsequent HPLC or GC/MS analysis. The highest values of methylated guanines were determined in the stomach and forestomach of the animals following both oral and inhalative exposure. These results demonstrate a systemic genotoxic effect of methyl iodide.
Subject(s)
DNA/metabolism , Hydrocarbons, Iodinated/metabolism , Adenine/isolation & purification , Administration, Inhalation , Administration, Oral , Animals , Carbon Radioisotopes , Chromatography, High Pressure Liquid/methods , DNA/isolation & purification , Female , Gastric Mucosa/metabolism , Guanine/isolation & purification , Hydrocarbons, Iodinated/administration & dosage , Hydrocarbons, Iodinated/pharmacokinetics , Hydrolysis , Liver/metabolism , Lung/metabolism , Male , Purines/isolation & purification , Rats , Rats, Inbred F344ABSTRACT
Ethylene oxide was incubated with different homobasic polynucleotides or dinucleotides. These were subsequently hybridized in equilibrium dialysis with their complementary or noncomplementary counterparts and the equilibrium constants determined. A change of the equilibrium constants after reaction with ethylene oxide corresponded with a shift in melting temperature of the reacted and hybridized macromolecular polynucleotides. The melting temperature was also changed when calf thymus DNA was reacted with ethylene oxide. In addition, the effect of ethylene oxide on the macromolecular single-stranded and double-stranded nucleic acids was investigated by studying the difference in rotation of circularly polarized light with the technique of circular dichroism spectroscopy. The changes in the spectra showed that ethylene oxide had altered the conformation of the hybridized double strands. These data indicated that binding sites in the pyrimidine bases of nucleic acid molecules, besides the previously known N-7 position in the purine base guanine, are attacked by ethylene oxide. There is evidence for the generation of N(4)-(2-hydroxyethyl)cytosine, O(2)-(2-hydroxyethyl)thymine and O(4)-(2-hydroxyethyl)uracil when the corresponding pyrimidine polynucleotides are incubated with ethylene oxide.
