Effect of butylated hydroxyanisole on the level of DNA adduction by aristolochic acid in the rat forestomach and liver.
Administration of butylated hydroxyanisole (BHA) orally at either 0.5 g or 1 g/kg daily for 14 days to rats did not produce any DNA adducts in the forestomach as measured by the 32P-postlabeling method using (1) limiting concentrations of 32P-ATP; (2) nuclease P1 enhancement; or (3) butanol extraction. Experiments were conducted to establish the effects of BHA administration on aristolochic acid (AA) DNA adduct formation in the forestomach and liver, when BHA was administered prior to, together with or after AA administration. Adduct levels per 10(9) nucleotides in the liver after oral dosing daily for 5 days with 1 mg/kg AA and BHA (1 g/kg) or corn oil (5 ml/kg) for 7 days were as follows: (a) BHA and AA given simultaneously; 235 +/- 71, (b) AA + corn oil; 63 +/- 39, (c) AA followed by BHA; 57 +/- 13, (d) AA followed by corn oil; 91 +/- 38, (e) BHA followed by AA; 90 +/- 12, (f) corn oil followed by AA; 83 +/- 24. For the forestomach the values were: (a) 236 +/- 86, (b) 77 +/- 25, (c) 367 +/- 97, (d) 296 +/- 47, (e) 217 +/- 81, (f) 70 +/- 64. These data suggest that BHA could have an enhancing effect on AA-induced lesions in the forestomach if dosed together with, or prior to, AA as adduct levels are significantly higher than in controls.
Routledge
M N
MN
Cancer Research Unit, University of York, Heslington, UK.
Orton
T C
TC
Lord
P G
PG
Garner
R C
RC
D000818:Animals; D034341:Aristolochic Acids; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010616:Phenanthrenes / Q000378:metabolism*; D051381:Rats; D013270:Stomach / Q000187:drug effects
D034341:Aristolochic Acids; D002273:Carcinogens; D010616:Phenanthrenes; D002083:Butylated Hydroxyanisole; D004247:DNA; C000228:aristolochic acid I