OBJECTIVES: Bisphenol A diglycidyl ether (BADGE) is the major component in commercial liquid epoxy resins, which are manufactured by co-reacting bisphenol A with epichlorohydrin. This study was performed to show the developmental effects of prenatal and postnatal exposures to BADGE in male rat offspring. METHODS: Mated female rats were divided into four groups, each containing 12 rats. The dosing solutions were prepared by thoroughly mixing BADGE in corn oil at the 0, 375, 1500 and 3000 mg/kg/day concentrations. Mated females were dosed once daily by oral gavage on gestation day (GD) 6 - 20 and postnatal day (PND) 0 - 21. Pregnant female dams were observed general symptoms and body weight. Also, male pups were observed the general symptoms, body weight, developmental parameters (e.g. anogenital distance, pina detachment, incisor eruption, nipple retention, eye opening, testis descent), organ pathologic changes and hormone levels of plasma. RESULTS: Pregnant rats treated with BADGE died at a rate of about 70% in the 1500 mg/kg/day group and all rats treated with 3000 mg/kg/day died. Body weight, for male pups treated with doses of 375 mg/kg/day, was significantly lower than in the control group at PND 42, 56, and 63 (p<0.05). Evaluation of body characteristics including; separation of auricle, eruption of incisor, separation of eyelid, nipple retention, descent of testis, and separation of the prepuce in the BADGE treated group showed no difference in comparisons with the control group. AGD and adjusted AGD (mm/kg) for general developmental items in BADGE 375 mg/kg/day treated pups tended to be longer than in controls, however, these differences were not statistically significant. Relative weights of adrenal gland, lung (p<0.05), brain, epididymis, prostate, and testis (p<0.01) were heavier than in control in measures at PND 9 weeks. There were no significant changes in comparisons of histological findings of these organs. Loss of spermatids was observed in the seminiferous tubule at PND 9 weeks, but no weight changes were observed. The plasma estrogen levels were similar in the control and treatment groups at PND 3, 6 and 9 weeks. The plasma testosterone levels in the control group tended to increase with age. However, in the BADGE 375 mg/kg/day treated male pups it did not tend to increase. CONCLUSIONS: These findings suggest that BADGE is a chemical that has developmental effects consistent with it being an endocrine disruptor.
Rats, Sprague-Dawley/growth & development ; Rats ; Pregnancy ; Male ; Korea ; Female ; Epoxy Compounds/administration & dosage/antagonists & inhibitors/*toxicity ; Carcinogens/administration & dosage/antagonists & inhibitors/*toxicity ; Animals

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent and prevalent nitrosamine procarcinogen found in cigarette smoke. The aim of this work is to study alterations in peroxiredoxin (Prx) expression induced by NNK during carcinogenesis. Characterization of Prx genes from hamster was performed using bioinformatics. V79 cells were induced with different concentrations of NNK (0.1-0.4 mg/mL), and the expression levels of six Prx genes (Prx1-Prx6) were measured by qRT-PCR 24 h following NNK treatment. Prx gene expression was induced by NNK stress, and the highest transcription levels were induced by over 20.42-fold relative to that of the control. NNK induced alterations in Prx expression over the course of lung cancer, which means Prxs may play important roles in ROS detoxification under NNK stress and their functions are complementary.
Animals ; Carcinogens ; administration & dosage ; toxicity ; Cell Line ; Cell Survival ; Cricetinae ; Cricetulus ; Dose-Response Relationship, Drug ; Gene Expression Regulation ; drug effects ; Nitrosamines ; administration & dosage ; toxicity ; Peroxiredoxins ; genetics ; metabolism

OBJECTIVETo evaluate the toxic and carcinogenic potential of ozone alone or in combination with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or dibutyl phthalate (DBP).

METHODSMale and female B6C3F1 mice were exposed, through inhalation, intravenous administration and diet, to 0.5 ppm of ozone, 1.0 mg/kg of NNK and 5000 ppm of DBP, individually and in combination for 16 and 32 weeks.

RESULTSNo treatment-related death was seen, but significant differences in body and organ weights between control and treated mice were observed during the study. No incidence of lung tumor incidence was recorded in mice exposed to either ozone alone or combined treatment. Oviductal carcinomas were observed in female mice exposed to ozone or DBP alone for 16 weeks and ozone in combination with NNK and DBP for 32 weeks.

CONCLUSIONAlthough ozone alone and in conjunction with NNK and/or DBP does not induce lung cancer under our experimental conditions, they induce oviductal carcinomas in B6C3F1 mice.

Adrenal Glands ; drug effects ; pathology ; Animals ; Carcinogens, Environmental ; administration & dosage ; toxicity ; Dibutyl Phthalate ; administration & dosage ; toxicity ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Kidney ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Lung ; drug effects ; pathology ; Male ; Mice ; Nitrosamines ; administration & dosage ; toxicity ; Organ Size ; Ovary ; drug effects ; pathology ; Ozone ; administration & dosage ; toxicity ; Sex Characteristics ; Testis ; drug effects ; pathology

OBJECTIVETo investigate the effect of sphingosine kinase 1 (SphK1) on the proliferation, apoptosis, migration and invasion of colon cancer TH-29 cells and to explore its molecular mechanisms.

METHODSPhorbol 12-myristate 13-acetate (PMA) was used to induce the activity of SphK1 and N, N-dimethylsphingosine (DMS) was used to suppress the activity of SphK1. Cell prolieration and apoptosis were detected by MTT assay and flow cytometry, respectively. The migration and invasion capabilities of the cells were assessed in Transwell chambers. The activity of SphK1 was assayed by autoradiography. Western blot was used to evaluate the protein expression of SphK1, p38, phosphorylated p38 (p-p38) and SAPK/JNK.

RESULTSPMA and DMS were able to induce and suppress the activity and protein expression of SphK1 in a time-dependent manner, respectively. PMA enhanced and DMS suppressed the cell viability in a time- and dose-dependent manner. Being treated with 100 nmol/L PMA or 50 µmol/L DMS for 0, 6, 12, 24 h, the cell apoptosis rates of PMA group were (9.35 ± 0.84)%, (7.61 ± 0.48)%, (5.53 ± 0.76)% and (0.56 ± 0.33)%, contrastly, that of DMS group were (9.18 ± 0.94)%, (12.06 ± 1.41)%, (19.80 ± 2.36)% and (31.85 ± 3.60)%, respectively. Compared with the control group, the cell migration and invasion capabilities of the PMA group were significantly enhanced, and that of the DMS group were significantly suppressed. The migration cell number of control, PMA and DMS groups were 68.75 ± 6.15, 109.33 ± 11.63 and 10.83 ± 2.48, the invasion cell number of control, PMA and DMS groups were 55.42 ± 4.50, 90.58 ± 7.06 and 9.58 ± 2.39, respectively. With the elevating activity and expression of SphK1, the protein expressions of p38, p-p38 and SAPK/JNK were strikingly suppressed. On the contrary, after treating with DMS the protein expressions of p38, p-p38 and SAPK/JNK were enhanced.

CONCLUSIONSSphK1 potently enhances the prolieration, migration and invasion of colon cancer HT-29 cells, meanwhile suppresses the cell apoptosis. The suppressing of the p38 and SAPK/JNK signalling pathways may be one of its molecular mechanisms.

Apoptosis ; drug effects ; Carcinogens ; administration & dosage ; pharmacology ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Enzyme Inhibitors ; administration & dosage ; pharmacology ; HT29 Cells ; Humans ; MAP Kinase Kinase 4 ; metabolism ; Neoplasm Invasiveness ; Phosphorylation ; Phosphotransferases (Alcohol Group Acceptor) ; metabolism ; physiology ; Sphingosine ; administration & dosage ; analogs & derivatives ; pharmacology ; Tetradecanoylphorbol Acetate ; administration & dosage ; analogs & derivatives ; pharmacology ; Time Factors ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVECalcium Glucarate (Cag), Ca salt of D-glucaric acid is a naturally occurring non-toxic compound present in fruits, vegetables and seeds of some plants, and suppress tumor growth in different models. Due to lack of knowledge about its mode of action its uses are limited in cancer chemotherapy thus the objective of the study was to study the mechanism of action of Cag on mouse skin tumorigenesis.

METHODSWe have estimated effect of Cag on DMBA induced mouse skin tumor development following complete carcinogenesis protocol. We measured, epidermal transglutaminase activity (TG), a marker of cell differentiation after DMBA and/or Cag treatment and [3H] thymidine incorporation into DNA as a marker for cell proliferation.

RESULTSTopical application of Cag suppressed the DMBA induced mouse skin tumor development. Topical application of Cag significantly modifies the critical events of proliferation and differentiation TG activity was found to be reduced after DMBA treatment. Reduction of the TG activity was dependent on the dose of DMBA and duration of DMBA exposure. Topical application of Cag significantly alleviated DMBA induced inhibition of TG. DMBA also caused stimulation of DNA synthesis in epidermis, which was inhibited by Cag.

CONCLUSIONCag inhibits DMBA induced mouse skin tumor development. Since stimulation of DNA synthesis reflects proliferation and induction of TG represents differentiation, the antitumorigenic effect of Cag is considered to be possibly due to stimulation of differentiation and suppression of proliferation.

9,10-Dimethyl-1,2-benzanthracene ; toxicity ; Administration, Topical ; Animals ; Anticarcinogenic Agents ; therapeutic use ; Carcinogens ; toxicity ; Cell Division ; drug effects ; DNA ; biosynthesis ; Enzyme Inhibitors ; toxicity ; Female ; Glucaric Acid ; therapeutic use ; Mice ; Skin Neoplasms ; chemically induced ; enzymology ; prevention & control ; Thymidine ; metabolism ; Transglutaminases ; metabolism

OBJECTIVESTo elucidate the possible involvement of monoamine neurotransmitters in the development of neurobehavioral damage produced by acrylonitrile in drinking water in male rat brains.

METHODSTotally 30 male SD rats were randomly divided into three groups, the control group (n = 10), low dosage group (n = 10), and high dosage group (n = 10), which were respectively administered 0 mg/L, 50 mg/L, 200 mg/L acrylonitrile (AN) in drinking water. The treatment was lasted for 12 weeks. Seven animals were randomly selected from each group for determination of monoamine neurotransmitters in striatum and cerebellum by high performance liquid chromatography with electrochemical detector and activities of monoamine oxidase in cortex.

RESULTSThe contents of dopamine in the striatum of low and high dosage groups were decreased to (2.2 +/- 0.7) and (3.2 +/- 2.0) microg/g wet tissue, respectively, and compared with that of control group (9.0 +/- 4.2) microg/g wet tissue, the differences were statistically significant. There were no statistical differences among the contents of dopamine in the cerebellum of all rats, and the levels of 3,4-dihydroxyphenylacetic acid (DOPAC), the major metabolite of dopamine in the cerebellum were (186 +/- 41), (245 +/- 90) and (115 +/- 65) ng/g wet tissue in the control, low and high dosage groups, respectively and in low-dosage group they were significantly higher than those in other groups. There was dosage-dependently decreasing of the contents of serotonin of striatum in the control (249 +/- 34) ng/g wet tissue, low dosage (155 +/- 95) ng/g wet tissue and high dosage groups (128 +/- 101) ng/g wet tissue.

CONCLUSIONThis study underlines the importance of alterations in the monoamine neurotransmitters system as a possible causative mechanism behind the behavioural and functional changes produced by acrylonitrile.

Acrylonitrile ; administration & dosage ; toxicity ; Animals ; Biogenic Monoamines ; metabolism ; Brain ; drug effects ; metabolism ; Carcinogens ; administration & dosage ; toxicity ; Cerebellum ; drug effects ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Corpus Striatum ; drug effects ; metabolism ; Dopamine ; metabolism ; Dose-Response Relationship, Drug ; Drinking ; Male ; Neostriatum ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism

AIMTo investigate the role of the Chinese herbal medicine Xianhuayin on the reversal of 7,12-dimethylbenz[a]anthracene (DMBA)-induced premalignant mucosal lesions in the oral buccal pouch of golden hamsters.

METHODOLOGYThe animals were randomly divided into a non-diseased control group (n=5) and an experimental group including 50 animals in which the buccal mucosa had been painted with DMBA (0.5% in acetone) to generate an oral mucosa premalignant lesion. Animals in the experimental group were further divided into Xianhuayin-treated group (n=30), untreated premalignant lesion group (n=10) and normal saline (NS)-treated group (n=10). The cheek (buccal) pouch mucosa of the golden hamsters in each group was observed with light and electron microscopy eight weeks after intragastric administration with NS or Xianhuayin.

RESULTSIn the non-diseased control group, the buccal mucosa was keratinized and stratified squamous epithelium under a light microscope. In the untreated premalignant lesion group, variable degrees of epithelial dysplasia was observed. The irregular epithelial mucosa gradually became distinct in the Xianhuayin-treated group. Scanning electronic microscopic (SEM) analysis showed that surface of the cells exhibited honeycomb structures in the hamster of untreated-group. The cells were morphologically irregular, overlapped and loosened in the untreated premalignant lesion group. Most of the cell surface exhibited honeycomb structure in the Xianhuayin-treated group. Transmission electronic microscopic (TEM) analysis showed that buccal mucosal epithelial cells were morphologically regular in the non-diseased control group. Desmosomes and tonofibrils were reduced and the nucleus was morphologically irregular in the untreated premalignant lesion group. In the Xianhuayin-treated group, the widening intercellular gap was gradually reduced, desmosomes and the cells becoming morphologically regular. No significant difference was observed between the hamsters in NS-treated group and those in the untreated premalignant lesion group. Significant therapeutic efficacy was observed in the group receiving Xianhuayin.

CONCLUSIONXianhuayin is effective in the reversal of DMBA-induced premalignant lesions in the buccal pouch of golden hamsters.

9,10-Dimethyl-1,2-benzanthracene ; adverse effects ; Amomum ; Animals ; Anticarcinogenic Agents ; administration & dosage ; therapeutic use ; Carcinogens ; Carthamus tinctorius ; Cell Nucleus ; drug effects ; Cricetinae ; Desmosomes ; drug effects ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Epithelial Cells ; drug effects ; Epithelium ; drug effects ; Glycyrrhiza ; Hyperplasia ; Intercellular Junctions ; drug effects ; Intermediate Filaments ; drug effects ; Keratins ; Mesocricetus ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Mouth Mucosa ; drug effects ; pathology ; Mouth Neoplasms ; prevention & control ; Philodendron ; Poria ; Precancerous Conditions ; prevention & control ; Random Allocation ; Sodium Chloride