Mutagenic potential of binary and complex mixtures using different enzyme induction systems.
A series of experiments was conducted to investigate the mutagenic potential of binary and complex mixtures in the presence and absence of inducible liver enzyme systems prepared with several different chemical inducers. Liver homogenate (S9, or 9000 x g supernatant) fractions were obtained from Sprague-Dawley rats induced with either Aroclor 1254 (AR), phenobarbital (PB), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or corn oil (UI). the mutagenic potential of test samples was measured with Salmonella typhimurium strain TA98 using each of the various S9 fractions. Test samples included benzo[a]pyrene (BaP), pentachlorophenol (PCP), a binary mixture of BaP and PCP, two five-component mixtures, a methylene chloride extract of wood preserving waste-amended soil, and a methanol extract of coal gasification waste. At a dose of 25 micrograms/plate, BaP produced 55, 83, 217, and 161 net revertants per plate with UI-, PB-, AR-, and TCDD-induced S9, respectively. The complex mixture extracted from the wood preserving waste-amended soil induced approximately equal responses with all four S9 mixes. At a dose of 250 micrograms/plate, the methanol extract of a coal gasification waste produced 56 net revertants using the uninduced S9; however, when Ar- and TCDD-induced S9 was used, 129 and 67 net revertants were observed, respectively. These data demonstrate the relative importance of the various induced cytochrome P-450 isozymes for the metabolism of mutagenic chemicals and complex mixtures.
Markiewicz
K V
KV
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, 77843-4458, USA.
Howie
L E
LE
Safe
S H
SH
Donnelly
K C
KC
D000818:Animals; D001711:Biotransformation; D004338:Drug Combinations; D004784:Environmental Monitoring / Q000379:methods; D004785:Environmental Pollutants / Q000633:toxicity*; D004790:Enzyme Induction; D006838:Hydrocarbons / Q000633:toxicity*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects
D004338:Drug Combinations; D004785:Environmental Pollutants; D006838:Hydrocarbons; D009153:Mutagens