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There has been considerable interest in the use of small fish models for detecting potential environmental carcinogens. In this study, both guppies (Poecilia reticulata) and medaka (Oryzias latipes) were exposed in the aquaria water to three known rodent carcinogens for up to 16 months. Nitromethane, which caused mammary gland tumors by inhalation exposure in female rats, harderian gland and lung tumors in male and female mice, and liver tumors in female mice by inhalation, failed to increase tumors in either guppies or medaka. Propanediol, which when given in the feed was a multisite carcinogen in both sexes of rats and mice, caused increased liver tumors in male guppies and male medaka. There was reduced survival in female guppies and no increased tumors in female medaka. 1,2,3-Trichloropropane, which when administered by oral gavage was a multisite carcinogen in both sexes of rats and mice, caused an increased incidence of tumors in the liver of both male and female guppies and medaka and in the gallbladder of male and female medaka. The results of this study demonstrate that for these three chemicals, under these specific exposure conditions, the fish appear less sensitive and have a narrower spectrum of tissues affected than rodents. These results suggest that fish models are of limited utility in screening unknown chemicals for potential carcinogenicity.

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Studies were conducted on two mutants of Escherichia coli that lack either glucosamine-6-phosphate deaminase or N-acetylglucosamine-6-phosphate deacetylase and which accumulate glucosamine-6-phosphate or N-acetylglucosamine-6-phosphate, respectively, when grown in the presence of N-acetylglucosamine. The addition of 10-4 to 10-a M N-acetylglucosamine to these mutant strains caused a rapid and complete inhibition of growth on substrates that enter the catabolic pathways at or below the level of fructose-6-phosphate. Growth on glucose was inhibited to a lesser degree, whereas only minor inhibition occurred when the pentoses were used as substrates. Growth on gluconate was found to be totally unaffected by these levels of N-acetylglucosamine. The objective of this investigation was to determine the nature of this "amino sugar sensitivity" phenomenon and the conditions under which it could be overcome. It was found that this amino sugar sensitivity was abolished when an exogenous source of pentose such as uridine was included in the culture medium. Experiments are described indicating that the accumulated amino sugar phosphate metabolites interfere with an early step in hexose metabolism of both mutants, resulting in a pentose deficiency and consequent inhibition of growth on certain substrates. MATERIALS AND METHODS Chemicals. 2,5-Diphenyloxazole (PPO) and 1,4bis-2-(4-methyl-5-phenyloxazolyl)-benzene (dimethyl POPOP) were products of Packard Instrument Co., Inc., Downers Grove, Ill. The following radiochemicals were purchased from the New England Nuclear Corp., Boston, Mass.: glucose-1-'4C, glucose-3,4-14C, glucose-6-'4C, gluconate-1-14C, gluconate-6-'4C, pyruvate-1-'4C, succinate-1, 4-14C, and "4C-leucine (U). Glucosamine (GN) and AcGN were purchased from Mann Research Laboratories, New York, N.Y. All other chemicals were of reagent grade and are readily available. Cultures and cultural conditions. The mutant strains used in this study were derived from the parental E.

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The composition, environmental fate, and effects of the polybrominated biphenyls (Firemaster BP-6 or FF-1) involved in the accidental contamination of cattle feed in Michigan in 1973 are reviewed. Toxic effects referred to in this report are limited to those occurring in domestic and laboratory animals and include general toxicity, neurobehavioral toxicity, immunotoxicity, reproductive toxicity, mutagenicity and carcinogenicity. The absorption, distribution, biotransformation and elimination of these polybrominated biphenyls are discussed along with the interactions with other chemicals and drugs.

Because of its function as transmitter of genetic information, DNA is the most important macromolecule in need of protection from attack by chemical and physical agents, but mechanisms have evolved for repairing such damage to DNA. The presence of the adaptive response and other cellular repair systems (excision, post-replication, SOS, etc.) diminishes the toxicologic effects of low doses of toxic or muta-genic substances. Whether or not these genotoxic effects can be reduced to undetectable levels is not certain. Nonetheless, this repair-mediated diminution of damage due to chemicals constitutes one of the arguments in favor of existence of “safe” threshold levels of chemical exposure (Schendel, 1981). In turn, the repair process itself may be affected by chemical and physical agents. To determine the mode of action of a specific compound on the process of DNA repair becomes complex when all factors are taken into consideration. There are agents which interfere with DNA repair but they are also as active or more active in suppressing replicative DNA synthesis, as well as RNA and protein synthesis. The interference with repair may arise from other major processes such as alteration of energy metabolism and effects on precursor pathways and/or enzymatic cofactors. Whether or not an agent can specifically inhibit DNA repair enzymes has not been answered. The point must be made, however, that this type of interference with essential protective mechanisms is taking place and it may change anticipated outcomes of chemical or physical exposures. The magnitude of this effect due to the exposure of people to so many chemicals should be recognized and studied for their degree of interference with all the processes of DNA repair.

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