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Rats treated with the carcinogen 2-acetylaminofluorene ( AAF) excrete major fractions of the administered compound in the urine as the N-, 3-, 5-, and 7-hydroxy derivatives ( 1-3) and in the bile as N-hydroxy-AAF( 4). The liver endoplasmic reticulum is a major site of the enzyme systems which perform these hydroxylations, all of which require T P N H and oxygen(5-7). The activity of the hepatic aromatic ring-hydroxylases increases approximately 1 0-fold when weanling rats are treated 24 hours prior to assay with 1 mg of 3-methylcholanthrene (MC) (5) , and administration of MC with AAF inhibits the carcinogenicity 'of AAF in the rat (8,s). Liver preparations from a variety of other rodent species also hydroxylate AAF (5-7).The relative amounts of ring-and N-hydroxylation of AAF are of importance, since ring-hydroxylation leads to non-carcinogenic metabolites ( 10-1 2 ) , while N-hydroxylation is *one of the steps required for activation of the amicle( 11,13). This paper presents data on the relative amounts of hydroxylation at the N-, 3-, 5-, and 7-positions of AAF by liver microsome preparations from weanling rodents either with or without prior treatment with MC. Marked species differences were found in the relative amounts of hydroxylation of AAF a t these positions before and after the administration of MC.Materials and methods. Animals. Male weanling animals were obtained from the following dealers in Madison, Wis.: albino rats, Holtzman Rat Co.; Syrian golden hamsters, Con Olson Co.; Ha,/ICR mice, A. R. Schmidt Co.; guinea pigs, O'Brien Co.; New Zealand rabbits, Willard Vass. They were fed ad libitum a grain diet( 14) which, for the guinea pigs, was supplemented with 1 g of ascorbic acidJkg. In those experiments in which puromycin or actinomycin D was injected, food was withheld from all animals after these injections were started.Chemicals. N-Hydroxy-AAF ( 1 1,l.S) , 2-acetylaminophenanthrene ( 16), and N-hydroxy-2-acetylaminophenanthrene ( 1 7) were synthesized in this laboratory. 7-Fluoro-AAF and its N-hydroxy derivative were generously furnished by Dr. T. Lloyd Fletcher, University at PENNSYLVANIA STATE UNIV on June 25, 2015 ebm.sagepub.com Downloaded from

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The effects of 22 herbicides on oxidative phosphorylation in mitochondria from cabbage (Brassica oleracea var. capitata L.) have been studied. Carbamates, phenoxyacids, 3,5-dimethyltetrahydro-l,3,5,2H-thiadiazine-2-thione (DMTT), N-1-napthylphthalamic acid (NPA), 2,3,6-trichlorobenzoic acid (2,3,6-TBA), 3-(p-chlorophenyl)-1,1-dimethylurea (monuron), and 2-chloro-2-N,N-diallylacetamide (CDAA) inhibited phosphorylation to a greater extent than oxygen uptake in cabbage mitochondria. The compounds 1,2-dihydropyridazine-3,6-dione (MH), 2,2-dichloropropionic acid (dalapon), 2,2,3-trichloropropionic acid (hereinafter referred to as 2,2,3-TPA), sodium chlorate, and 3-amino-l,2,4-triazole (amitrole) at concentrations as high as 1 × 10–2 M did not have a large effect on oxidative phosphorylation in cabbage mitochondria. Respiration which was stimulated by 2,4-dinitrophenol (DNP) or adenosine diphosphate (ADP) was inhibited by 2,4-dichlorophenoxyacetic acid (2,4-D). Although 2,4-D did not affect Mg++-stimulated adenosine triphosphatase (ATPase), it inhibited an oleate-stimulated ATPase activity and the ATP-32Pi exchange reaction in cabbage mitochondria. The results suggest that 2,4-D may inhibit respiration in cabbage mitochondria by an effect on a reaction involved in coupling phosphorylation with electron transport.

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