Biological Monitoring of Exposure to Cisplatin in Rats Using SOS Chromotest

2000 ◽  
Vol 19 (1) ◽  
pp. 13-17
Author(s):  
Sang-Jun Lee ◽  
Jang-Hyun Hur ◽  
Byung-Hoon Lee

Cisplatin (CDDP) is a potent antitumor drug used in the treatment of a variety of solid tumors. The purpose of the present study was to establish screening biomarker of exposure to CDDP using SOS chromotest. The ultimate goal of this screen is to facilitate the choice of an effective drug and the prognosis of the therapy. In the current screening protocol, the SOS chromotests were performed on the urine of Sprague-Dawley rats administered intravenously with CDDP. Urine samples were collected individually in the metabolic cage at 6 (U0–6) and 12 hours (U6–12) after treatment and were tested their DNA damaging effects. The urine samples obtained from the rats administered with 1 mg/kg CDDP did not induce SOS response in our experimental conditions. At a dose of 5 mg/kg, two out of five rat showed more than 50% increase in the DNA damaging effect compared to that of the control. The genotoxic effect was observed only in the U0–6, whereas the U6–12 were not genotoxic but cytotoxic to the test strain. Similar results were obtained at a dose of 10 mg/kg: 5 out of 10 rats showed SOS response and the U6–12 were also proven to be cytotoxic. These results suggest that the method presented in this study could be used as a biomarker of exposure to CDDP.

Toxics ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 31
Author(s):  
Alejandro Monserrat García-Alegría ◽  
Agustín Gómez-Álvarez ◽  
Iván Anduro-Corona ◽  
Armando Burgos-Hernández ◽  
Eduardo Ruíz-Bustos ◽  
...  

Recently, soluble forms of aluminum for human use or consumption have been determined to be potentially toxic due to their association with hepatic, neurological, hematological, neoplastic, and bone conditions. This study aims to assess the genotoxic effect of aluminum chloride on genomic instability associated with the onset of N-nitroso-N-methylurea (NMU)-induced breast cancer in Sprague Dawley rats. The dietary behavior of the rats was assessed, and the concentration of aluminum in the mammary glands was determined using atomic absorption spectroscopy. Genomic instability was determined in the histological sections of mammary glands stained with hematoxylin and eosin. Moreover, micronucleus in peripheral blood and comet assays were performed. The results of dietary behavior evaluation indicated no significant differences between the experimental treatments. However, aluminum concentration in breast tissues was high in the +2000Al/−NMU treatment. This experimental treatment caused moderate intraductal cell proliferation, lymph node hyperplasia, and serous gland adenoma. Furthermore, micronucleus and comet test results revealed that +2000Al/−NMU led to a genotoxic effect after a 10-day exposure and the damage was more evident after a 15-day exposure. Therefore, in conclusion, genomic instability is present and the experimental conditions assessed are not associated with breast cancer.


1995 ◽  
Vol 11 (2) ◽  
pp. 119-149 ◽  
Author(s):  
Fiorella Belpoggi ◽  
Morando Soffritti ◽  
Cesare Maltoni

In the framework of a series of experiments conducted to evaluate the carcinogenic effects of oxygenated gasoline additives, MTBE was analyzed in an oral lifetime carcinogenicity study using 8-week-old male and female Sprague- Dawley rats. These experiments were part of a large research project on gasoline carcinogenicity performed at the Bentivoglio (BT) Castle Cancer Research Center of the Ramazzini Foundation and of the Bologna Institute of Oncology. MTBE, dissolved in oil, was administered by stomach tube at the doses of 1000, 250, or 0 mg/kg b.w., once daily, four days weekly, for 104 weeks. The animals were maintained until natural death. The last animal died 166 weeks after the start of the experiment, i.e., at 174 weeks of age. Under the tested experimental conditions, MTBE was shown to cause an increase in Leydig interstitial cell tumors of the testes and a dose-related increase in lymphomas and leukemias in female rats.


2019 ◽  
Author(s):  
Fabien Naneix ◽  
Sophie C. Pinder ◽  
Megan Y. Summers ◽  
Renee M. Rouleau ◽  
Eric Robinson ◽  
...  

ABSTRACTIn studies of eating behavior that have been conducted in humans, the tendency to consume more when given larger portions of food, known as the portion size effect (PSE), is one of the most robust and widely replicated findings. Despite this, the mechanisms that underpin it are still unknown. In particular, it is unclear whether the PSE arises from higher-order social and cognitive processes that are unique to humans or, instead, reflects more fundamental processes that drive feeding, such as conditioned food-seeking. Importantly, studies in rodents and other animals have yet to show convincing evidence of a PSE. In this series of studies, we used several methods to test for a PSE in adult male Sprague Dawley rats. Our approaches included using visually identifiable portions of a palatable food; training on a plate cleaning procedure; providing portion sizes of food pellets that were signaled by auditory and visual food-predictive cues; providing food with amorphous shape properties; and providing standard chow diet portions in home cages. In none of these manipulations did larger portions increase food intake. In summary, our data provide no evidence that a PSE is present in male Sprague Dawley rats, and if it is, it is more nuanced, dependent on experimental procedure, and/or smaller in size than it is in humans. In turn, these findings suggest that the widely-replicated PSE in humans may be more likely to reflect higher-order cognitive and social processes than fundamental conditioned behaviors.HighlightsPortion size effect (PSE) refers to increased food intake induced by large portions.Although widely replicated in human feeding studies, it may not exist animals.Presence of a PSE in animals would shed light on mechanisms, which are not known.Here, we find no evidence of PSE in male Sprague Dawley rats under a number of experimental conditions.This suggests that the human PSE is more likely due to socio-cognitive processes.


1980 ◽  
Vol 30 (3) ◽  
pp. 723-727
Author(s):  
R W Bolton

Sprague-Dawley rats which produce "naturally occurring" antibodies to glycerol teichoic acid (GTA) displayed immunosuppression of anti-sheep erythrocyte plaque-forming cell and serum antibody responses when a single dose of lipid-free GTA was administered 24 h before immunization. Such suppression was enhanced by administering GTA complexed with anti-GTA immunoglobulin G. Animals fed a GTA-free diet produced no anti-GTA immunoglobulins and failed to show GTA-mediated immunosuppression under similar experimental conditions. However, when those animals were given GTA-anti-GTA complexes, suppression was evident. The results suggested antigenic competition mediated by immune complex-activated suppressor T cells. Lipid-free GTA did not stimulate serum antibody responses under the experimental conditions employed.


1986 ◽  
Vol 250 (6) ◽  
pp. R1108-R1116 ◽  
Author(s):  
J. E. Cox ◽  
J. F. Lorden

We assessed the effect of scapular brown adipose tissue (BAT) denervation on dietary obesity in adult female Sprague-Dawley rats. In rats maintained for 32 days on an obesity-inducing regimen, BAT denervation produced significant reductions in food intake (83.4 vs. 94.4 kcal/day), weight gain (66.0 vs. 103.5 g), and carcass fat (19.3 vs. 27.6%). A subgroup of denervates consuming as many calories as controls (94.1 kcal/day) failed to gain more weight (92.2 g) or accumulate more fat (25.4%) than controls. In rats developing obesity for 32 days followed by 8 days on laboratory chow, weight change was unaffected by denervation during either weight gain (89.4 vs. 87.1 g for controls) or weight loss (21.2 vs. 22.1 g) phases, as was carcass fat (21.0 vs. 20.4%). BAT norepinephrine utilization was unchanged in nondenervated obese rats and those recovering from obesity. We did not, therefore, find evidence that under these experimental conditions sympathetic activation of BAT countered obesity during overconsumption or contributed to recovery from obesity.


2016 ◽  
Vol 33 (4) ◽  
pp. 365-372 ◽  
Author(s):  
Xue Luo ◽  
Lingjuan Ma ◽  
Peng Gao ◽  
Yanwen Zhang

The objective of the present study was to systematically determine the effects of 50 Hertz (Hz) magnetic fields (MFs) on biochemical parameters in rats. Sixty-four adult (5 weeks old, 140–165 g) male Sprague–Dawley rats were randomly divided into four groups: sham, 20 µTesla (µT), 100 µT, and 500 µT 50 Hz MF ( n = 16 in each group). The rats in the MF groups were exposed for 2 h daily for up to 4 weeks. Under these experimental conditions, body weight, organ coefficients, biochemical parameters (blood lipids, myocardial enzymes, liver function, and renal function) were measured. We found that 50 Hz MFs had no significant effects on growth or on the majority of blood biochemical parameters, with the exception of creatinine and cholesterol. However, the changes in creatinine and cholesterol were relatively small and unlikely to be clinically relevant.


Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs

Investigation of the spontaneous pituitary adenomas in rat have been limited mainly to light microscopic study. Furth et al. (1973) described them as chromophobic, secreting prolactin. Kovacs et al. (1977) in an ul trastructural investigation of adenomas of old female Long-Evans rats, found that they were composed of prolactin cells. Berkvens et al. (1980) using immunocytochemistry at the light microscopic level, demonstrated that some spontaneous tumors of old Wistar rats could contain GH, TSH or ACTH as well as PRL.


Author(s):  
F. G. Zaki ◽  
E. Detzi ◽  
C. H. Keysser

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.


Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs

Gonadotroph cell adenomas of the pituitary are infrequent in human patients and are not invariably associated with altered gonadal function. To date, no animal model of this tumor type exists. Herein, we describe spontaneous gonadotroph cell adenomas in old male and female Sprague-Dawley rats by histology, immunocytology and electron microscopy.The material consisted of the pituitaries of 27 male and 38 female Sprague Dawley rats, all 26 months of age or older, removed at routine autopsy. Sections of formal in-fixed, paraffin-embedded tissue were stained with hematoxylin-phloxine-saffron (HPS), the PAS method and the Gordon-Sweet technique for the demonstration of reticulin fibers. For immunostaining, sections were exposed to anti-rat β-LH, anti-ratβ-TSH, anti-rat PRL, anti-rat GH and anti-rat ACTH 1-39. For electron microscopy, tissue was fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4 and embedded in epoxy-resin. Tissue fixed in 10% formalin, embedded in epoxy resin without osmification, was used for immunoelectron microscopy.


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