Promotion of liver and kidney carcinogenesis by ethyl tertiary-butyl ether (ETBE) in male Wistar rats.

Tumor-promoting effects of ethyl tertiary-butyl ether (ETBE) were investigated in a 2-stage carcinogenesis bioassay with regard to hepatic and renal carcinogenesis in rats. Male 6-week-old Wistar rats were given drinking water containing N-ethyl-N-(2-hydroxyethyl)nitrosamine (EHEN), as an initiator, at a dose of 500 ppm for 2 weeks. Starting one week thereafter, the animals were administered ETBE at dose levels of 0 (control), 100, 300, 500 or 1,000 mg/kg/day by gavage for 19 weeks from week 4 to 22.

Immunohistochemical characteristics of surfactant proteins a, B, C and d in inflammatory and tumorigenic lung lesions of f344 rats.

Surfactant proteins (SPs), originally known as human lung surfactants, are essential to respiratory structure and function. There are 4 subtypes, SP-A, SP-B, SP-C and SP-D, with SP-A and SP-D having immunological functions, and SP-B and SP-C having physicochemical properties that reduce the surface tension at biological interfaces. In this experiment, the expressions of SP-A, SP-B, SP-C and SP-D in lung neoplastic lesions induced by N-bis (2-hydroxypropyl) nitrosamine (DHPN) and inflammatory lesions due to quartz instillation were examined and compared immunohistochemically.

Multigenerational effects of whole body exposure to 2.14 GHz W-CDMA cellular phone signals on brain function in rats.

The present experimental study was carried out with rats to evaluate the effects of whole body exposure to 2.14 GHz band code division multiple access (W-CDMA) signals for 20 h a day, over three generations. The average specific absorption rate (SAR, in unit of W/kg) for dams was designed at three levels: high (<0.

Comparative study of toxic effects of anatase and rutile type nanosized titanium dioxide particles in vivo and in vitro.

Two types of nanosized titanium dioxide, anatase (anTiO2) and rutile (rnTiO2), are widely used in industry, commercial products and biosystems. TiO2 has been evaluated as a Group 2B carcinogen. Previous reports indicated that anTiO2 is less toxic than rnTiO2, however, under ultraviolet irradiation anTiO2 is more toxic than rnTiO2 in vitro because of differences in their crystal structures.

No Promoting Effect of Ethyl Tertiary-butyl Ether (ETBE) on Rat Urinary Bladder Carcinogenesis Initiated with N-Butyl-N-(4-hydroxybutyl)nitrosamine.

The effects of ethyl tertiary-butyl ether (ETBE) on two-stage urinary bladder carcinogenesis in male F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were investigated at various dose levels with regard to possible promoting activity. Groups of 30 rats were given drinking water containing 500 ppm BBN, as an initiator, for 4 weeks and starting one week thereafter received ETBE by gavage (daily, 7 days/week) at dose levels of 0 (control), 100, 300, 500 or 1000 mg/kg/day until experimental week 36. No statistically significant differences in incidences of preneoplastic lesions, papillomas, and carcinomas of the urinary bladder were evident in rats treated with 100-1000 mg/kg/day ETBE as compared with control values.

Arachidonate-enriched triglyceride oil does not promote tumor development in a rat medium-term multi-organ carcinogenesis model.

The modifying potential on tumor development of arachidonate-enriched triglyceride oil (ARA-oil) containing approximately 40% arachidonic acid was investigated in a medium-term multi-organ carcinogenesis bioassay using male and female F344 rats. The animals were sequentially given five carcinogens with different target sites in the first 4 weeks, and then administered ARA-oil for 24 weeks at dietary levels of 0% (control), 1.25%, 2.

Concordance between Results of Medium-term Liver Carcinogenesis Bioassays and Long-term Findings for Carcinogenic 2-Nitropropane and Non-carcinogenic1-Nitropropane in F344 Rats.

This study was conducted to determine the concordance of results for a pair of structural isomers, 2-nitropropane (2-NP) and 1-nitropropane (1-NP), using the rat medium-term liver carcinogenesis bioassay (Ito test) and previously published long-term carcinogenicity tests. Male F344 rats were given a single intraperitoneal injection of DEN (200 mg/kg b.w.

Medium-term multi-organ carcinogenesis bioassay of ethyl tertiary-butyl ether in rats.

The modifying potential of ethyl tertiary-butyl ether (ETBE) on tumor development was investigated in a medium-term multi-organ carcinogenesis bioassay using male F344 rats. Animals were sequentially given 5 carcinogens with different target sites in the first 4 weeks for multi-organ initiation. After one week they received ETBE by gavage at dose levels of 0 (control), 300 or 1000mg/kg/day until experimental week 28.

Lack of promoting effect of titanium dioxide particles on ultraviolet B-initiated skin carcinogenesis in rats.

Titanium dioxide (TiO(2)) is used in sunscreens and cosmetics as an ultraviolet light screen. TiO(2) has carcinogenic activity in the rat lung, but its effect on the skin has not been reported. We examined the promoting/carcinogenic effect of nano-size TiO(2) particles using a two-stage skin model.

Lack of skin carcinogenicity of topically applied titanium dioxide nanoparticles in the mouse.

This study was conducted to examine the post-initiation carcinogenic potential of coated and uncoated titanium dioxide nanoparticles (CTDN and UCTDN) using a mouse medium-term skin carcinogenesis bioassay. For this purpose, 5, 10 and 20mg/animal doses of CTDN or UCTDN were applied to mouse skin in the post-initiation phase (up to 20 weeks) in a two-stage skin carcinogenesis model using 7 week old CD1 (ICR) female mice. 7,12-dimethylbenz[a]anthracene (DMBA) and 12-o-tetradecanoylphorbol 13-acetate (TPA) were used as the initiator and a positive control promoter, respectively.

A 90-day oral toxicity study of nisin A, an anti-microbial peptide derived from Lactococcus lactis subsp. lactis, in F344 rats.

This study was designed to evaluate and characterize any adverse effect of nisin A, when administered to both sexes of F344/DuCrlCrlj rats (10 males and 10 females in each group) at dietary levels of 0%, 0.2%, 1.0% and 5.

Involvement of macrophage inflammatory protein 1alpha (MIP1alpha) in promotion of rat lung and mammary carcinogenic activity of nanoscale titanium dioxide particles administered by intra-pulmonary spraying.

Titanium dioxide (TiO(2)) is evaluated by World Health Organization/International Agency for Research on Cancer as a Group 2B carcinogen. The present study was conducted to detect carcinogenic activity of nanoscale TiO(2) administered by a novel intrapulmonary spraying (IPS)-initiation-promotion protocol in the rat lung. Female human c-Ha-ras proto-oncogene transgenic rat (Hras128) transgenic rats were treated first with N-nitrosobis(2-hydroxypropyl)amine (DHPN) in the drinking water and then with TiO(2) (rutile type, mean diameter 20 nm, without coating) by IPS.

A medium-term, rapid rat bioassay model for the detection of carcinogenic potential of chemicals.

The Ito Liver Model and the Ito Multi-organ Model are used in conjunction and constitute an efficient and rapid bioassay for the identification of both genotoxic and nongenotoxic carcinogenic chemicals. The Ito Liver Model is an 8-week bioassay system that uses the number and size of foci of hepatocytes positive for glutathione S-transferase placental form (GST-P) as the end-point marker. One hundred fifty-nine compounds were tested using the Ito Liver Model: 61 of 66 hepatocarcinogens tested positive, and 10 of 43 nonliver carcinogens were also positive.

Rat medium-term multi-organ carcinogenesis bioassay of Agaricus blazei Murrill fruit-body extract.

The modifying potential of Agaricus blazei Murrill fruit-body extract (ABFE) on tumor development was investigated in a medium-term multi-organ carcinogenesis bioassay. Male 6-week-old F344 rats were treated with N-nitrosodiethylamine (DEN), N-methyl-N-nitrosourea (MNU), 1,2-dimethylhydrazine dihydrochloride (DMH), N-butyl-N-(hydroxybutyl)-nitrosamine (BBN), and diisopropanolnitrosamine (DHPN) for initiation (DMBDD treatment). After a 1-week withdrawal period, the animals received distilled water (vehicle control) or ABFE A, gamma-amino butyric acid (GABA) at 0.

Effects of N-acetylcysteine, quercetin, and phytic acid on spontaneous hepatic and renal lesions in LEC rats.

The effects of anti-oxidants were examined in Long-Evans Cinnamon (LEC) rats, which develop acute hepatic injury, and subsequent hepatic and renal tumors due to accumulation of excess Cu. The rats, at the age of 15 weeks, were supplied a diet containing either 1% of N-acetylcysteine (NAC), quercetin (QC), or phytic acid (PA), or basal diet alone. At weeks 2 and 6 posttreatment, animals were sacrificed for collection of blood and tissue samples.

Lack of enhancing effects of sodium nitrite on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis in female Sprague-Dawley rats.

A number of heterocyclic amines (HCAs) have been shown to exert enhanced carcinogenic and mutagenic potential when given simultaneously with sodium nitrite (NaNO(2)). In the present experiment, effects of combined treatment with NaNO(2) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the most prevalent carcinogenic HCAs in the human environment, were assessed with regard to mammary tumor induction in female Sprague-Dawley (SD) rats. Animals at 6 weeks of age were given intragastric doses of 100mg/kg body weight of PhIP twice a week for 4 weeks, during which period 0 or 0.

Lack of potential of low dose N-nitrosodimethylamine to induce preneoplastic lesions, glutathione S-transferase placental form-positive foci, in rat liver.

Induction of liver lesions in male F344 rats by the genotoxic and carcinogenic N-nitrosodimethylamine (NDMA) was studied at a wide range of dose levels, i.e. from 0.

Potent chemopreventive agents against pancreatic cancer.

Development of pancreatic cancers is clinically so silent in general that at the time of diagnosis, the vast majority of cases are incurable with a very poor prognosis. Therefore, effective preventive approaches against this aggressive disease are urgently required. Experimentally, carcinogenesis process is assumed to consist of at least two stages named initiation and promotion.

Sequential alteration of apoptosis, p53 expression, and cell proliferation in the rat pancreas treated with 4-hydroxyaminoquinoline 1-oxide.

Changes in p53 expression, apoptosis and cell proliferation after treatment with 4-hydroxyaminoquinoline 1-oxide (4HAQO) were investigated in the rat pancreas and liver, target and nontarget organs for tumorigenesis, respectively. Male rats were given a single intravenous injection of 4HAQO at a dose of 20 mg/kg body weight and control rats received vehicle alone and were euthanized after 2-72 hours. Pancreata and livers were removed for histopathological examination, immunohistochemistry for p53 protein, PCNA and Ki-67, and TUNEL labeling and electron microscopic observation for detecting apoptosis.

A 13-week subchronic toxicity study of paprika color in F344 rats.

The fruit of the paprika (Capsicum annuum) has been widely used in various countries as a spice and food-coloring additive. As a part of the safety assessment of paprika color (Paprika oleoresin), a 13-week subchronic toxicity study was performed in F344 rats. To establish a no-observed-adverse-effect level (NOAEL) for application in subsequent long-term studies, rats were fed powder diet containing paprika color at dose levels of 0 (basal diet), 0.

Lack of Carcinogenic Sensitivity of the Glandular Stomach in Heterozygous p53 Knockout Mice Given N-Methyl-N-Nitrosourea in their Drinking Water for 26 Weeks.

Gastric tumorigenic sensitivity to N-methyl-N-nitrosourea (MNU) was examined in heterozygous p53 knockout (p53(+/-)) CBA mice and their wild-type littermates (p53(+/+)). In Experiment 1, 37 male p53(+/-) or 38 male p53(+/+) CBA mice were given MNU in their drinking water at concentration of 50ppm (Group 1 or 4), 10ppm (group 2 or 5) or 0ppm (group3 or 6) for 26 weeks. In Experiment 2, p53(+/-) and p53(+/+) CBA mice of both sexes received water containing 50ppm MNU for 26 weeks.

Chemoprevention of lung carcinogenesis by cacao liquor proanthocyanidins in a male rat multi-organ carcinogenesis model.

The effects of cacao liquor proanthocyanidins (CLPr) on tumorigenesis were investigated using a multi-organ carcinogenesis model in male F344 rats receiving combined treatment with a single i.p. injection of diethylnitrosamine (100 mg/kg body wt), four i.

Lack of initiation activity in rat liver of low doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline.

It has been generally accepted that genotoxic carcinogens have no threshold in exerting their potential for cancer induction. However, the non-threshold theory can be challenged for cancer risk assessment in humans. Here we examined low dose carcinogenicity of a food-derived, genotoxic hepatocarcinogen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), using an in vivo medium-term bioassay to detect initiating activity for rat hepatocarcinogenesis.

A cyclooxygenase-2 inhibitor, nimesulide, inhibits postinitiation phase of N-nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis in hamsters.

The modification effects of nimesulide, a cyclooxygenase (COX)-2 inhibitor, administration during the postinitiation phase of pancreatic carcinogenesis were investigated in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Male Syrian hamsters were given 4 weekly s.c.

Effects of cigarette smoke and a heterocyclic amine, MeIQx on cytochrome P-450, mutagenic activation of various carcinogens and glucuronidation in rat liver.

In order to elucidate the mechanism underlying enhancement by cigarette smoke (CS) of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-induced rat hepatocarcinogenesis, hepatic levels of cytochrome P-450 (CYP) enzymes, mutagenic activation of various carcinogens and UDP-glucuronyltransferase (UDPGT) activities were assayed in male F344 rats. Immunoblot analyses for microsomal CYP proteins revealed induction of CYP1A1 and constitutive CYP1A2 (2.3- to 2.