Aspirin intake suppresses MMC-induced genotoxicity in mice.

The genotoxicity induced by mitomycin C (MMC) was found to be decreased by aspirin on alkaline single cell gel electrophoresis (SCG) assay in multiple organs of mice. Aspirin at doses of 0.5, 5 and 50 mg/kg and MMC at 2 mg/kg were administered and then liver, lung, kidney, spleen, colon and bone marrow were sampled after 3 h. Significant protective effects of aspirin against MMC-induced genotoxicity was observed in all but the bone marrow, where no change was evident. The results suggest that the radical scavenging ability of aspirin prevents danage by MMC-induced reactive oxygen species (ROS) in multiple organs.

Morphine does no promote esophageal carcinogenesis in rats exposed to diethylnitrosamine

BACKGROUND: The high incidence of esophageal cancer in the north of Iran has been associated to the consumption of opium and exposure to nitrosamines. Diethylnitrosamine has an established potential of producing experimental cancer in the esophagus and liver. AIM: To evaluate by histopathology the effect of oral administration of morphine and diethylnitrosamine during 23 weeks on the hepatic and esophageal carcinogenesis on 176 rats. METHODS: We divided the rats into the following groups: Morph: morphine; Den: diethylnitrosamine; Den+morph: Den and morphine in the same solution; Den/morph: Den and morphine in different solutions and days. RESULTS: Morphine did not promote neoplasias. The highest neoplastic incidents were found: a) in the esophagus, Den in relation to Den/morph and Den+morph (71.1 percent, 55.8 percent, and 50.0 percent); b) in the liver, Den and Den/morph in relation to Den+morph (73.8 percent, 81.4 percent, and 40.9 percent); c) higher incident of hepatic neoplasia than esophageal in Den/morph (81.4 percent and 55.8 percent). Different doses of diethylnitrosamine were ingested among the groups Den, Den/morph, and Den+morph, respectively 2.9, 2.8, and 2.3 mg/kg/day. CONCLUSIONS: These results show that the morphine did not promote esophageal carcinogenesis and may have stimulated the hepatic metabolism of the first pass of the carcinogen.

RACIONAL: A alta incidência de câncer esofagiano no norte do Irã foi associada ao consumo de ópio e exposição às nitrosaminas. A dietilnitrosamina possui potencial estabelecido de produzir câncer experimental em esôfago e fígado. OBJETIVO: Avaliar por histopatologia o efeito da administração oral de morfina e de dietilnitrosamina na carcinogênese esofágica e hepática em ratos. MÉTODOS: Durante 23 semanas, 176 ratos ingeriram diferentes soluções, sendo divididos em grupos: Morf: morfina; Den: dietilnitrosamina; Den+morf: dietilnitrosamina e morfina numa mesma solução; Den/morf: dietilnitrosamina e morfina em diferentes soluções e dias. RESULTADOS: Morf não promoveu neoplasias. Encontraram-se maiores incidências neoplásicas: a) no esôfago, Den em relação à Den/morf e Den+morf (71,1 por cento, 55,8 por cento e 50,0 por cento); b) no fígado, Den e Den/morf em relação à Den+morf (73,8 por cento, 81,4 por cento e 40,9 por cento); c) maior incidência de neoplasia hepática do que esofágica em Den/morf (81,4 por cento e 55,8 por cento). Diferentes doses de dietilnitrosamina foram ingeridas entre os grupos Den, Den/morf e Den+morf, respectivamente 2,9, 2,8 e 2,3 mg/kg/dia. CONCLUSÕES: A morfina não promoveu a carcinogênese esofágica e pode ter estimulado o metabolismo hepático de primeira passagem do carcinógeno.

Inducing mutations in the mouse genome with the chemical mutagen ethylnitrosourea

When compared to other model organisms whose genome is sequenced, the number of mutations identified in the mouse appears extremely reduced and this situation seriously hampers our understanding of mammalian gene function(s). Another important consequence of this shortage is that a majority of human genetic diseases still await an animal model. To improve the situation, two strategies are currently used: the first makes use of embryonic stem cells, in which one can induce knockout mutations almost at will; the second consists of a genome-wide random chemical mutagenesis, followed by screening for mutant phenotypes and subsequent identification of the genetic alteration(s). Several projects are now in progress making use of one or the other of these strategies. Here, we report an original effort where we mutagenized BALB/c males, with the mutagen ethylnitrosourea. Offspring of these males were screened for dominant mutations and a three-generation breeding protocol was set to recover recessive mutations. Eleven mutations were identified (one dominant and ten recessives). Three of these mutations are new alleles (Otop1mlh, Foxn1sepe and probably rodador) at loci where mutations have already been reported, while 4 are new and original alleles (carc, eqlb, frqz, and Sacc). This result indicates that the mouse genome, as expected, is far from being saturated with mutations. More mutations would certainly be discovered using more sophisticated phenotyping protocols. Seven of the 11 new mutant alleles induced in our experiment have been localized on the genetic map as a first step towards positional cloning.

Impact of hypercholesterolemia on in vitro toxicity of N-nitrosodiethylamine: effect on lipidperoxidation of blood and tissue.

In vitro treatment of erythrocytes of normal and hypercholesterolemic rats with N-nitrosodiethylamine (NDEA), an important carcinogen frequently present in human environment and food chain resulted in a marginal increase in osmotic fragility of erythrocytes without affecting their antioxygenic potential as evidenced by insignificant effect on lipid peroxidation (LPO). However, (LPO) of all the tissues (heart, lung, liver, kidney and spleen) increased significantly on in vitro treatment with NDEA. The effects were different in different tissues under different dietary conditions

Hepatic and renal oxidative stress in acute toxicity of N-nitrosodiethylamine in rats.

Nitrosoamines such as N-nitrosodiethylamine (NDEA) produce oxidative stress due to generation of reactive oxygen species and may alter antioxidant defence system in the tissues. NDEA was administered ip as a single dose to rats in LD50 or in lower amounts and the animals were sacrificed after 0-48 hr of treatment. The results showed that lipid peroxidation in liver increased, however no significant increase in kidney LPO was observed after NDEA administration. Superoxide dismutase (SOD) and glutathione reductase (GSH-R) activity increased in liver, however, catalase (CAT) activity in liver was inhibited in NDEA treated rats. Kidney showed an increase in SOD activity after an initial decrease along with increase in GSH-R activity in NDEA treated rats. However, kidney CAT activity was not significantly altered in NDEA intoxicated rats. Serum transaminases, serum alkaline phosphatase blood urea nitrogen, serum creatinine and scrum proteins were elevated in NDEA treated rats. The results indicate NDEA-induced oxidative stress and alteration in antioxidant enzymes in liver and kidney to neutralise oxidative stress.