Formation of DNA adducts in F-344 rats after oral administration or inhalation of [14C]methyl bromide.
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.
Gansewendt
B
B
Institut für Arbeitsphysiologie, Universität Dortmund, Germany.
Foest
U
U
Xu
D
D
Hallier
E
E
Bolt
H M
HM
Peter
H
H
D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005753:Gastric Mucosa / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D006842:Hydrocarbons, Brominated / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors; D013270:Stomach / Q000187:drug effects*
D002250:Carbon Radioisotopes; D006842:Hydrocarbons, Brominated; D006147:Guanine; D004247:DNA; C008449:O-(6)-methylguanine; C005218:methyl bromide