Metabolism of the carcinogen 7-methylbenz[c]-acridine in the rat

Abstract

1. The biliary excretion of radioactivity by adult Wistar rats given i.v. 7-methyl-[7-¹⁴C]benz[c]acridine(¹⁴C-7-MBAC) and [methyl-³H]-7-methylbenz[c]acridine (³H-7-MBAC) (2 mg/kg) was 61% and 48%, respectively, in males in six hours. Females excreted 33% of a 2 mg/kg dose of ³H-7-MBAC in the same time-period.

2. For male rats, the urinary and faecal excretions were about 10% and 61% of the dose of ¹⁴C-7-MBAC, respectively, in seven days. No enterohepatic circulation could be demonstrated in control male rats.

3. The biliary excretion of radioactivity by phenobarbital- and 3-methylcholanthrene-induced male rats given ¹⁴C-7-MBAC was similar to or greater than that of control male rats.

4. The organo-soluble biliary metabolites after β-glucuronidase/arylsulphatase hydrolysis were separated by h.p.l.c., and quantitative metabolite distributions were obtained for induced and control rats by comparison with metabolite standards.

5. The mutagenicity of bilt from carcinogen-dosed control rats was greater than that of equivalent bile from carcinogen-dosed 3-methylcholanthrene-pretreated animals.