RESUMEN
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a food-borne mutagen and carcinogen that induces tumors of the colon and the prostate gland in male rats and of the mammary gland in female rats. In this study we describe the frequency and specificity of PhIP-induced mutations in the cecum, proximal colon and distal colon of male and female lacI transgenic rats. This is the first report of mutational data from discrete regions of the colon. After 61 days of treatment with 200 p.p.m. PhIP mixed into the diet, PhIP-induced mutant frequencies were elevated 7-fold in the cecum and 14- to 21-fold in the colon of male and female rats compared with untreated controls. PhIP-induced mutant frequencies increased significantly (overall trend, P < 10(-4)) along the length of the colon of both males and females, with cecum < proximal colon < distal colon. A total of 754 PhIP mutants (363 male, 391 female) were sequenced to provide the mutational spectra for each of the three tissue sections from males and females. These mutational spectra consisted predominantly of G:C-->T:A and G:C-->C:G transversions and deletions of G:C base pairs. There were no significant differences between the mutational spectra with respect to sex or position in the colon. Therefore, we surmise that following induction of mutations by PhIP in male and female colons, non-mutagenic factors, possibly hormonal, preferentially influence the formation of tumors in the colon of male rats.
Asunto(s)
Proteínas Bacterianas/genética , Ciego/efectos de los fármacos , Colon/efectos de los fármacos , Proteínas de Escherichia coli , Imidazoles/toxicidad , Mutación/efectos de los fármacos , Mutación/genética , Proteínas Represoras/genética , Animales , Animales Modificados Genéticamente , Proteínas Bacterianas/metabolismo , Ciego/metabolismo , Colon/metabolismo , Ingestión de Alimentos/efectos de los fármacos , Femenino , Represoras Lac , Masculino , Pruebas de Mutagenicidad/métodos , Mutágenos/toxicidad , Ratas , Ratas Endogámicas F344 , Proteínas Represoras/metabolismoRESUMEN
Mutational spectra provide a powerful approach to investigate both the mutagenic potential and the mechanism of action of suspected mutagens and carcinogens. Recently, transgenic techniques have made it possible to generate mutational spectra in animals. Such a spectrum may consist of 50 to 200 mutants depending on the nature of the mutations, and many spectra can be generated depending on the design of the experiment. This report describes a practical approach for the processing and sequencing of large numbers of lacI mutants recovered from Big Blue animals.
Asunto(s)
Animales Modificados Genéticamente/genética , Proteínas Bacterianas/genética , Proteínas de Escherichia coli , Mutación , Proteínas Represoras/genética , Análisis de Secuencia de ADN/métodos , Animales , Proteínas Bacterianas/química , Metodologías Computacionales , Represoras Lac , Ratones , Ratones Transgénicos , Reacción en Cadena de la Polimerasa/métodos , Ratas , Proteínas Represoras/química , Análisis de Secuencia de ADN/instrumentaciónRESUMEN
As part of the National Pesticide Monitoring Program, the U.S. Fish and Wildlife Service analyzed organochlorine contaminant residues in fish samples collected from about 100 stations each year from 1970 to 1974. During this period, mean residues of DDT and its metabolites declined nationally but remained widespread, and high concentrations continued to be present in areas where DDT use was extensive. Results of interlaboratory crosscheck analyses supported these conclusions, despite interpretation problems posed by intercompound analytical interferences in 1970 and 1971. Temporal trends in PCB residues were less obvious. Highest PCB residues were found in the industrialized areas of the Northwest and Midwest, and traces were present at most stations. Dieldrin and endrin residues remained essentially unchanged during this period; dieldrin residues were widespread and were highest in Hawaii and in areas of the Midwest where aldrin was used extensively. Toxaphene occurrence increased; it was formerly found only in fish from streams draining cotton-farming regions, but residues were detected in 1974 samples from other areas. According to the recommendation of the National Academy of Sciences' Water Quality Criteria, organochlorine residues in freshwater fish may have represented a hazard to piscivorous fish and wildlife at 71 percent of the stations sampled in 1970 and 66 percent in 1974.
Asunto(s)
Peces/metabolismo , Insecticidas/análisis , Residuos de Plaguicidas/análisis , Bifenilos Policlorados/análisis , Contaminantes Químicos del Agua/análisis , Contaminantes del Agua/análisis , Animales , Arocloros/análisis , DDT/análisis , Contaminación de Alimentos , Factores de Tiempo , Toxafeno/análisis , Estados UnidosRESUMEN
As part of the National Pesticide Monitoring Program, the Fish and Wildlife Service, U.S. Department of Interior, analyzed selected fish samples from 100 monitoring stations for residues of mercury, arsenic, lead, cadmium, or selenium in 1971-73. At most stations, detectable residues of all metals were present in more than 95 percent of the composite samples. Fishes with mercury residues exceeding 0.5 mg/kg wet weight in the whole fish were mainly predators. Fishes with residues of arsenic, lead, cadmium, and selenium exceeding 0.5 mg/kg included predatory and nonpredatory species. The number of composite samples in which residues of these elements exceeded 0.5 mg/kg decreased from 1971 to 1973, whereas the percentage of samples with detectable residues increased slightly. Only selected samples were analyzed in 1973; therefore, these figures should be used only cautiously as trend data. Species of fish collected varied considerably between geographic regions but were similar from year to year within each region.