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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.