Formation and fate of nucleic acid and protein adducts derived from N-nitroso-bile acid conjugates.
14C-N-Nitrosoglycocholic acid (14C-NOGC) reacted with calf thymus DNA in vitro to give a number of carboxymethylated adducts (7-carboxymethylguanine [7-CMG], 3-carboxy-methyladenine [3-CMA] and O6-carboxymethylguanine [O6-CMG]). 7-CMG is excreted unchanged in urine, and its use as a marker for NOGC exposure was studied. Administration of 14C-NOGC results in a dose-dependent urinary excretion of 14C-7-CMG and in labelling of blood proteins, albumin and globin. The activity in albumin disappears in vivo, with a half-life very similar to that of albumin itself. The monitoring of carboxymethylated nucleic acid bases and proteins appears to be a useful way of monitoring endogenous formation of NOGC and related compounds.
Shuker
D E
DE
MRC Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, UK.
Howell
J R
JR
Street
B W
BW
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D009603:Nitroso Compounds / Q000493:pharmacokinetics*
D001647:Bile Acids and Salts; D001798:Blood Proteins; D009603:Nitroso Compounds; D004247:DNA