In contrast to vertebrates and to bacteria relatively little is known about the metabolism of invertebrates (1). For a better understanding of comparative biochemistry information about this subject is required. Furthermore, investigations of the biochemical characteristics of parasitic invertebrates will reveal metabolic reactions essential for survival of these organisms. Information obtained from such studies will make it possible to search for non-toxic inhibitors of essential metabolic reactions and eventually may afford a possibility of replacing the presently prevailing empirical methods with a more rational development of chemotherapeutic agents against pathogenic parasites. ~c c o r d i n g l y , when an investigation concerned with the chemotherapy of schistosomiasis was initiated in this laboratory, it was decided to study the metabolism of Schistosoma mansoni, an organism concerned with the pathogenesis of one form of this disease. Materials and MethodsThe schistosomes were removed with the aid of dissecting needles from the mesenteric and portal veins of mice infested with Schistosoma mansoni. The infestation had been produced by the intraperitoneal injection of 125 to 150 cercariae per mouse 6 to 10 weeks previously. The cercariae were obtained from shedding snails (Australorbis glabratus). The latter were either naturally infested snarls collected in Puerto Rico or they had been infested by exposure to miracidia from eggs present in the livers of mice with sehistosomiasis.~ The sehistosomes were placed in a medium of the following composition: 0.137 r~ NaC1, 0.0085 ~ KC1, 0.0003 ~r CaCI~, 0.005 ~ MgCI~, and 0.06 sodium phosphate or glycylglycine buffer. The pH of this solution was 7.7. After several washings with this medium, 10 to 25 pairs of worms were transferred into 0.8 ml. of medium contained in a Warburg respirometer vessel (total volume of vessel: 4 to 5 ml.). Incubation was carried out at 37.5°C. for a period of 2 hours. After several * The major part of the investigation described in this paper was carried out with the aid of a

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The effects of dietary administration of 3,5-di-tert-butyl-4-hydroxytoluene (BHT), 2(3)-tert-butyl-4-hydroxyanisole (BHA), ethoxyquin (EQ) and 5-(2-pyrizinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz) on aflatoxin B1 (AFB1) - DNA adduct formation in vivo in livers and kidneys of rats were investigated. Male F344 rats were treated with 1 mg/kg AFB1 by i.p. administration and nucleic acids isolated 2 h post dosing. Animals were fed a semipurified diet supplemented with either 0.5% EQ, 0.45% BHT, 0.45% BHA or 0.1% oltipraz for 2 weeks prior to AFB1 treatment. Analysis of nucleic acid bases by h.p.l.c. showed that several AFB1 metabolite-DNA adducts were formed in both tissues. The principal and related adducts of 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 represented approximately 80-90% of all adducts in both tissues and in all treatment groups. However, inclusion of the antioxidants in the diet resulted in substantial reductions in overall AFB1 modified DNA levels. EQ, BHT, BHA and oltipraz reduced the covalent binding of AFB1 to liver DNA by 91, 85, 65 and 76% and to kidney DNA by 80, 35, 62 and 64%, respectively. Concordantly, the specific activities of hepatic enzymes of presumed importance to AFB1 detoxification, epoxide hydrase, and glucuronyl and glutathione transferases were significantly elevated by all antioxidants. Reduced glutathione levels were unchanged except by oltipraz, although activities of enzymes contributing to the maintenance of reduced glutathione pools, glutathione reductase and glucose-6-phosphate dehydrogenase, were elevated in most treatment groups. An excellent correlation (r = 0.95) was observed between the degree of inhibition of DNA binding by AFB1 and the induction of hepatic glutathione S-transferase activities by the four antioxidants.