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microsome system: activation of anthraquinone glucosides by gut bacterial enzymes
69 7 R. Schoeny, J.C. Loper and C.C. Smith, Departments of Microbiology and Environmental Health, University o f Cincinnati Medical Center, Cincinnati, Ohio (U.S.A.)
Rat liver induction by representative chlorinated hydrocarbons as determined by bacterial mutagenesis The polychlorinated biphenyl mixture Aroclor 1254 (PCB) is widely used as a general inducer of mixed function oxidases in in vitro testing for chemical mutagens. This study compares the inductive effects of stable (mirex, MRX, and kepone, KPN), and more rapidly metabolized chlorinated hydrocarbons (1,2,4-trichlorobenzene, TCB). Male 150-g Sprague-Dawley rats were treated by i.p. injection of corn oil solutions of one of the c o m p o u n d s according to the following schedule: PCB, 50 mg/kg for 5 days; TCB, 50 or 200 mg/kg for 4 days or 200 mg/kg for 2 days; KPN 18, 25, 36 or 50 mg/kg for 2 days; MRX 25 or 100 mg/kg for 2 days. Control animals received 2 ml/kg corn oil (CO) for 4 days. Animals were starved 24 h prior to kill. Toxicity was observed only with the KPN-treated rats. Inductive effects were monitored b y relative liver weights and by activation of 2-aminoanthracene (2AA), b e n z o [ a ] p y r e n e and aflatoxin B1 to mutagens for Salmonella typhimurium tester strains T A 1 5 3 8 and TA100. Relative liver weights increased in this order: PCB = TCB > MRX ~ KPN ~> CO. KPN, MRX, and TCB were not detected as mutagens either directly or in the presence of PCB- or homologously-induced S-9. To date KPN has n o t been detected as an inducer. Inductive effects of mirex are variable. 2AA mutagenesis is dramatically affected by the a m o u n t of S-9 used for activation. CO S-9 gives peak activation for mutagenesis of T A 1 0 0 at both low and high amounts of S-9 while PCB S-9 activation drops off rapidly with increasing S-9 concentration. L o w concentrations of TCB-induced S-9 increased 2AA mutagenicity.
8 J.P. Brown, G.W. R o e h m and R.J. Brown, Dynapol, Palo Alto, Cal. 94304
(U.S.A.) Mutagenicity of anthraquinones in the Salmonella/microsome system: activation of anthraquinone glucosides by gut bacterial enzymes Anthraquinone (AQ) derivatives have been used as colorants in foods, drugs, cosmetics, hair dyes and textiles. A survey of AQ mutagenicity in short-term microbial tests has so far included over 120 compounds. In this report Salmonella mutagenicity data on a b o u t 30 AQ's are presented. Notable among these are 7 hydroxy-AQ's and 8 AQ-glucones o f plant and microbial origin, and 4 dialkylaminoalkylamino-AQ's that have been shown to interact with DNA in vitro. Of the hydroxy-AQ's the most mutagenic (revertants/nmol) for the Salmonella tester strains were Lucidin (1,3-dihydroxy-2-hydroxymethyl-AQ) and its co-ethyl ether with values of 62 and 72, respectively, for strain T A 1 0 0 plus
Rat liver induction by representative chlorinated hydrocarbons as determined by bacterial mutagenesis The polychlorinated biphenyl mixture Aroclor 1254 (PCB) is widely used as a general inducer of mixed function oxidases in in vitro testing for chemical mutagens. This study compares the inductive effects of stable (mirex, MRX, and kepone, KPN), and more rapidly metabolized chlorinated hydrocarbons (1,2,4-trichlorobenzene, TCB). Male 150-g Sprague-Dawley rats were treated by i.p. injection of corn oil solutions of one of the c o m p o u n d s according to the following schedule: PCB, 50 mg/kg for 5 days; TCB, 50 or 200 mg/kg for 4 days or 200 mg/kg for 2 days; KPN 18, 25, 36 or 50 mg/kg for 2 days; MRX 25 or 100 mg/kg for 2 days. Control animals received 2 ml/kg corn oil (CO) for 4 days. Animals were starved 24 h prior to kill. Toxicity was observed only with the KPN-treated rats. Inductive effects were monitored b y relative liver weights and by activation of 2-aminoanthracene (2AA), b e n z o [ a ] p y r e n e and aflatoxin B1 to mutagens for Salmonella typhimurium tester strains T A 1 5 3 8 and TA100. Relative liver weights increased in this order: PCB = TCB > MRX ~ KPN ~> CO. KPN, MRX, and TCB were not detected as mutagens either directly or in the presence of PCB- or homologously-induced S-9. To date KPN has n o t been detected as an inducer. Inductive effects of mirex are variable. 2AA mutagenesis is dramatically affected by the a m o u n t of S-9 used for activation. CO S-9 gives peak activation for mutagenesis of T A 1 0 0 at both low and high amounts of S-9 while PCB S-9 activation drops off rapidly with increasing S-9 concentration. L o w concentrations of TCB-induced S-9 increased 2AA mutagenicity.
8 J.P. Brown, G.W. R o e h m and R.J. Brown, Dynapol, Palo Alto, Cal. 94304
(U.S.A.) Mutagenicity of anthraquinones in the Salmonella/microsome system: activation of anthraquinone glucosides by gut bacterial enzymes Anthraquinone (AQ) derivatives have been used as colorants in foods, drugs, cosmetics, hair dyes and textiles. A survey of AQ mutagenicity in short-term microbial tests has so far included over 120 compounds. In this report Salmonella mutagenicity data on a b o u t 30 AQ's are presented. Notable among these are 7 hydroxy-AQ's and 8 AQ-glucones o f plant and microbial origin, and 4 dialkylaminoalkylamino-AQ's that have been shown to interact with DNA in vitro. Of the hydroxy-AQ's the most mutagenic (revertants/nmol) for the Salmonella tester strains were Lucidin (1,3-dihydroxy-2-hydroxymethyl-AQ) and its co-ethyl ether with values of 62 and 72, respectively, for strain T A 1 0 0 plus