DNA bases attack by reactive metabolites produced during carbon tetrachloride biotransformation and promotion of liver microsomal lipid peroxidation.
Free radicals produced during carbon tetrachloride biotransformation and the promoted lipid peroxidation process of liver microsomal lipids are able to attack the DNA bases guanine, cytosine and thymine to give at least three altered bases. They were identified as 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua); 5-hydroxycytosine (5OHCyt) and 5-hydroxymethyluracil (5OHMeU). No adenine adducts were detected. If these altered bases were formed during carbon tetrachloride poisoning and were not adequately repaired before cell replication, serious permanent consequences for liver cell DNA could be expected and this might be somehow involved in the liver carcinogenic effects of the haloalkane.
Castro
G D
GD
Centro de Investigaciones Toxicológicas (CEITOX)-CITEFA/CONICET, Pica. de Buenos Aires, Argentina.
Díaz Gómez
M I
MI
Castro
J A
JA
D000818:Animals; D001711:Biotransformation; D002251:Carbon Tetrachloride / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000633:toxicity; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D006147:Guanine / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010432:Pentoxyl / Q000031:analogs & derivatives / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013941:Thymine / Q000378:metabolism
D018736:DNA Adducts; D011743:Pyrimidines; D017392:Thiobarbituric Acid Reactive Substances; C071023:2,6-diamino-4-hydroxy-5-formamidopyrimidine; C025280:trichloromethyl free radical; C008055:5-hydroxymethyluracil; D006147:Guanine; C017400:5-hydroxycytosine; D010432:Pentoxyl; D003596:Cytosine; D002251:Carbon Tetrachloride; D013941:Thymine