Suppression of arylamine toxicity in the Fischer-344 rat following ingestion of a complex mixture.
The toxic effects of a mixture of 2-aminoanthracene (2-AA), benzanthracene (BA), and dinitropyrene isomers (DNP), and the toxic effects of these compounds individually, were investigated in the Fischer-344 rat following dietary exposure via a powdered basal diet. Animals were sacrificed at 14-, 30-, and 80-days of dietary exposure. Exposure to dietary 2-AA alone induced anorexia, cachexia, variable mortality, and altered serum chemistry profiles in the F-344 rat. Reduced lymphocyte counts were also shown in rats exposed to 2-AA. A temporal pattern of effect of 2-AA dietary exposure was observed in the progression of hepatic lesions in exposed animals. Dietary exposure to either DNP isomers or BA at a 10-fold higher concentration in the diet, relative to 2-AA, did not induce detectable toxic responses. However, exposure of rats to a mixture of 2-AA, BA, and DNP isomers (100 mg/kg, 1.0 g/kg, and 1.0 g/kg of diet, respectively) resulted in the attenuation of toxic effects when compared to exposure of F-344 rats to 2-AA alone. These results indicate that the toxic effects of 2-AA are suppressed by co-administration of DNP and BA and suggest that compound interactions need to be considered when predicting the toxic potential of specific environmental pollutants.
Boudreau
M D
MD
Department of Physiology, Pharmacology, and Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803, USA.
Baker
D G
DG
Taylor
H W
HW
Barker
S A
SA
Means
J C
JC
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000873:Anthracenes / Q000633:toxicity*; D001219:Aspartate Aminotransferases / Q000097:blood; D001551:Benz(a)Anthracenes / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D004032:Diet; D004336:Drug Antagonism; D007536:Isomerism; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008136:Longevity / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011721:Pyrenes / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000187:drug effects / Q000473:pathology
D000873:Anthracenes; D001551:Benz(a)Anthracenes; D011721:Pyrenes; C006593:2-anthramine; C030935:benz(a)anthracene; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase