A study of 2,4,6-trinitrotoluene inhibition of benzo[a]pyrene uptake and activation in a microbial mutagenicity assay.
A number of in vitro and in vivo studies have determined that binary and complex mixtures may interact to produce a toxicity that could not be predicted based on the individual chemicals. The present study was conducted with a binary mixture of model compounds to investigate possible interactions affecting their mutagenicity. The compounds included Benzo[a]pyrene (BAP), a polycyclic aromatic hydrocarbon that is an indirect-acting mutagen of great environmental concern, and 2,4,6-Trinitrotoluene (TNT), a nitro-aromatic compound that is a direct-acting mutagen frequently found as a soil contaminant at munitions sites. This study indicated that a binary mixture of BAP and TNT failed to induce the positive mutagenic response in Salmonella typhimurium strain TA98 characteristic of either compound alone. Spectrofluorometric analysis of BAP, and kinetic analyses of 3HBAP uptake in the presence or absence of TNT using TA98 cells that were treated or untreated with activated rat liver microsomes were performed. In cells preloaded with BAP, cellular BAP fluorescence was rapidly suppressed in the presence of TNT. Mass spectroscopy of BAP and TNT mixtures revealed a number of products, believed to be the result of complexation and nitration, that may account for the antagonistic action of TNT on BAP-induced mutagenicity in TA98 cells. Further, kinetic studies indicated that TNT inhibited the incorporation of BAP into cells.
Washburn
K S
KS
Department of Veterinary Anatomy and Public Health, Texas A & M University, College Station 77843-4458, USA.
Donnelly
K C
KC
Huebner
H J
HJ
Burghardt
R C
RC
Sewall
T C
TC
Claxton
L D
LD
D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002274:Carcinogens, Environmental / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D007700:Kinetics; D008862:Microsomes, Liver; D051381:Rats; D012486:Salmonella typhimurium; D013050:Spectrometry, Fluorescence; D014303:Trinitrotoluene / Q000737:chemistry / Q000494:pharmacology*
D002274:Carcinogens, Environmental; D014303:Trinitrotoluene; D001564:Benzo(a)pyrene