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Results for “Butylhydroxybutylnitrosamine”

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At least 19 recordsLinked to original sources

PubMed1997

Chemopreventive effects of diosmin and hesperidin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary-bladder carcinogenesis in male ICR mice.

The chemopreventive effects of 2 flavonoids (diosmin and hesperidin) on N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced urinary-bladder carcinogenesis were examined in male ICR mice. Animals were divided into 11 groups, and groups 1 to 7 were given OH-BBN (500 ppm) in the drinking water for 6 weeks. Groups 2 to 4 were fed diets containing the test compounds (group 2, 1000 ppm diosmin; group 3, 1000 ppm hesperidin; group 4,900 ppm diosmin + 100 ppm hesperidin) for 8 weeks during the initiation phase, while groups 5 to 7 were fed these diets, respectively, for 24 weeks during the post-initiation phase. Groups 8 to 11 were controls, given only the test compounds or untreated basal diets throughout the experiment (weeks 1 to 32). The incidence of bladder lesions and cell-proliferation activity estimated by enumeration of silver-stained nucleolar-organizer-region-associated proteins (AgNORs) and by the 5-bromodeoxyuridine (BUdR)-labeling index was compared among the groups. Feeding of the test compounds, singly or in combination, during both phases caused a significant reduction in the frequency of bladder carcinoma and preneoplasia. Dietary administration of these compounds significantly decreased the AgNOR count and the BUdR-labeling index of various bladder lesions. These findings suggest that the flavonoids diosmin and hesperidin, individually and in combination, are effective in inhibiting chemical carcinogenesis of the bladder, and that such inhibition might be partly related to suppression of cell proliferation.

Administration, Oral↗

PubMed1998

Strong promoting activity of phenylethyl isothiocyanate and benzyl isothiocyanate on urinary bladder carcinogenesis in F344 male rats.

Post-initiation effects of phenylethyl isothiocyanate (PEITC) and benzyl isothiocyanate (BITC) on hepatocarcinogenesis and urinary bladder carcinogenesis were examined in rats pretreated with diethylnitrosamine (DEN) and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Groups of 21 rats received a single intraperitoneal injection of 200 mg/kg body weight of DEN. Starting 2 days thereafter, they were administered 0.05% BBN in the drinking water for 4 weeks. Three days after completion of the carcinogen treatment, they were placed on a diet containing PEITC or BITC at a dose of 0.1%, or a basal diet alone for 32 weeks and then killed for autopsy. Further groups of 6 rats each were similarly treated with PEITC, BITC or basal diet alone for 32 weeks without prior DEN and BBN exposure. In the liver, although the incidences of liver tumors were not significantly affected, the multiplicity of foci larger than 0.5 cm in diameter was slightly increased by PEITC. In the urinary bladder, the incidences of papillary or nodular (PN) hyperplasias and carcinomas were significantly elevated by PEITC or BITC after DEN and BBN initiation. In the groups without initiation, PN hyperplasia was found in all rats of both PEITC and BITC groups, along with papillomas and carcinomas in some animals. Tumors and PN hyperplasias in the groups treated with PEITC and BITC are characterized by downward growth. Our results thus showed PEITC and BITC to be strong promoters of urinary bladder carcinogenesis with some complete carcinogenic potential.

Animals↗

PubMed1999

A functional and quantitative mutational analysis of p53 mutations in yeast indicates strand biases and different roles of mutations in DMBA- and BBN-induced tumors in rats.

In order to analyze the mutational events and to understand the biological significance of the p53 gene in chemical carcinogenesis, we applied a new yeast-based p53 functional assay to ovarian tumors induced by 7, 12-dimethylbenz[a]anthracene (DMBA), as well as to transitional cell carcinomas of the urinary bladder induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in rats. The assay demonstrated that 15 of 19 DMBA induced tumors harbored clonal p53 mutations, which is consistent with the expectations of the "clonal expansion" hypothesis. The majority of the mutations were purine (AG) to pyrimidine (CT) transversions (12/19) on the non-transcribed (sense) strand (NTS), which is likely to be due to depurination created by DMBA adduct formation on the NTS. In contrast, we found no pyrimidine to purine [corrected] transversion on the NTS. After cessation of BBN treatment, BBN-induced multifocal lesions in the bladder contained heterogeneous p53 mutations at an early stage. In the later stage, however, clonal p53 mutations were identified in 4 out of 7 bladders analyzed, conforming with the concept of "field cancerization". The observed base substitutions were G-->A (1/6) or C -->T transitions (2/6), and mutations at T (3/6) on the NTS in clonal mutations, together with non-clonal mutations, showing a preference of C-->T to G-->A (17 vs. 0). Thus, preferential repair was found in the transcribed strand of the p53 gene, whether modified by DMBA or by BBN carcinogens. Very similar mutation patterns were observed between clonal and non-clonal mutations in the DMBA- and BBN-induced tumors, indicating that the rat yeast p53 functional assay can be a potential tool for the characterization of in vivo mutation patterns of p53, when modified by chemical carcinogens.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1998

Frequent p53 mutations and occasional loss of chromosome 4 in invasive bladder carcinoma induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in B6D2F1 mice.

B6D2F1 mice (45/group) were treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) or uracil as follows: Group 1 received 0.05% BBN in drinking water for the entire experiment, Group 2 received 5 mg of BBN by gastric gavage in 0.1 mL of 20% ethanol twice per week for 10 wk, Group 3 received a 2.5% uracil-containing diet for the entire experiment, and Group 4 was controls (received 0.1 ml of 20% ethanol by gavage twice per week for 10 wk). The surviving mice in Group 1 were killed after week 26 and those in the other groups after week 30. By week 15, three of 11 Group 1 and one of 15 Group 2 mice had bladder carcinoma. By 26 and 30 wk, respectively, invasive carcinomas were observed in 33 of 34 and six of 21 mice in Groups 1 and 2 and renal pelvic carcinomas in 11 of 34 and three of 21 mice in Groups 1 and 2. Four of 19 uracil-treated mice had bladder nodular hyperplasia. By polymerase chain reaction-single-strand conformation polymorphism and sequence analyses, 16 of 20 and two of five bladder carcinomas from Groups 1 and 2, respectively, showed mutations in the p53 gene. Ha-ras mutation was present in one case. Loss of heterozygosity analysis with simple-sequence length polymorphism markers for chromosome 4 showed that 10 of 21, two of 15, and nine of 13 mice in Groups 1-3, respectively, had heterozygous or homozygous deletions. B6D2F1 mice are therefore susceptible to the urothelial carcinogenic effects of BBN and develop frequent p53 mutations and chromosome 4 deletions. Chromosome 4 deletions were also seen with uracil.

Animals↗

PubMed1999

A comparative analysis of allelic imbalance events in chemically induced rat mammary, colon, and bladder tumors.

In this paper, patterns of allelic imbalances (Als) in chemically induced rat mammary, colon, and bladder tumors from (Wistar Furth x Fischer 344)F1 rats are described and compared. Male F1 rats were administered azoxymethane (AOM), and colon tumors were collected at 58 wk after treatment. Female F1 rats were given either N-nitroso-N-methylurea (NMU) or N-butyl-(hydroxybutyl)-nitrosoamine (BBN), and mammary and bladder tumors were collected at 15 and 52 wk after treatment, respectively. DNA was extracted from a subset of 18 of the largest tumors from each group, and a genome scan was performed by using polymerase chain reaction and 90 polymorphic microsatellite markers. Als, such as loss of heterozygosity, gene duplication, and microsatellite instability, were observed at low frequencies in all of the tumor models. Thirty random Als were observed in the AOM-induced colon tumors but only four in the NMU-induced mammary tumors. In both these models, all the tumors were classified as adenocarcinomas, and most of the Als observed were confined to single tumors with atypical histopathology. In contrast, 27 random Als were identified in the BBN-induced bladder tumors. Als were observed in both transitional-cell carcinomas and papillomas, although most were in the carcinomas. Statistical analysis of the Al data revealed no significant nonrandom Als within or among the tumor models, although several of the infrequently observed Al events identified in the rat tumors may also be observed in the corresponding human tumor type.

Alleles↗

PubMed1998

F344/Shi rats bearing type b catalase-1 locus are sensitive to sodium L-ascorbate promotion of two-stage urinary bladder carcinogenesis.

Our previous data showed that F344/DuCrj and LEW/Crj rat strains bearing the type a catalase-1 locus (CS1a) are sensitive to the promoting activity of sodium L-ascorbate (Na-AsA) in 2-stage urinary bladder carcinogenesis, whereas ODS/Shi and WS/ Shi rat strains bearing the type b catalase-1 locus (CS1b) are resistant. In present study, we investigated the susceptibility of F344/Shi rats also bearing the CS1 to the Na-AsA-promoting effects on bladder tumor development. Male rats, 6 weeks old, were given 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water for 4 weeks, then fed either basal diet supplemented with 5% Na-AsA or no chemicals for 32 weeks. The rats given BBN alone had a few small carcinomas in the urinary bladder. In contrast, animals administered BBN-Na-AsA had many large carcinomas. Administration of Na-AsA was associated with significant elevation of urinary pH and L-ascorbic acid. The results indicate that F344/Shi rats are sensitive to the promoting effects of Na-AsA on 2-stage urinary bladder carcinogenesis, and thus that the CS1 locus may not influence susceptibility to promotion.

Alleles↗

PubMed1998

Possible rare involvement of O6-methylguanine formation as a significant mutational factor in mouse urinary bladder carcinogenesis models.

O6-methylguanine is known as one of the major premutagenic lesions in the human and rodent carcinogenesis process. O6-methylguanine-DNA methyltransferase (MGMT), which repairs methylated guanine bases, might prevent the G:C to A:T transition, and transgenic mice carrying this MGMT gene have been reported to be less sensitive to the carcinogenicity of certain alkylating agents. Here we utilized MGMT transgenic mice to assess the significance of O6-methylguanine formation during urinary bladder carcinogenesis. In experiment 1, 100 and 60 ppm N-butyl-N(4-hydroxybutyl)nitrosamine was given for 20 weeks to transgenic and non-transgenic mice in their drinking water. The incidences of urinary bladder carcinomas were not different between transgenic mice and non-transgenic mice. The mutational spectrum of the p53 gene was evaluated by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. The pattern of p53 mutations of transgenic and non-transgenic mice did not differ, and the frequencies of mutations were 40% and 42%, respectively. G:C to A:T transition mutations were particularly infrequent (1 of 14 mutations, 7%). In experiment 2, N-methyl-N-nitrosourea, which might induce O6-methylguanine in affected alleles, was given once a week, 3 times (total 5 mg) by direct instillation into the urinary bladder through an abdominal incision. No significant neoplastic lesions were detected, although the experiment was limited by severe toxicity of the treatment. p53 immunostaining was done and there was no difference in transgenic and non-transgenic mice. These results suggest that O6-methylguanine formation might not be a significant mutational factor in these mouse urinary bladder carcinogenesis models.

Adenosine Deaminase↗

PubMed1999

Hepatocarcinogenic activity of N-butyl-N-(4-hydroxybutyl)nitrosamine in rats is not modified by sodium L-ascorbate.

Male F344 and Wistar Shionogi (WS) rats were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 20 weeks and then killed at week 36 (experiment 1). Although reduction of body weight increase was found, no effects on liver weights were noted. Formalin-fixed and paraffin-embedded liver tissues from rats killed terminally were cut and stained for glutathione S-transferase placental form (GST-P) immunohistochemically. Marked elevation of quantitative values of small GST-P positive (GST-P+) foci were apparent in both strains of rat administered BBN. In experiment 2, both sexes of F344 rats were given 0.05% BBN in the drinking water for 4 weeks and then fed diet containing 0 or 5.0% sodium L-ascorbate (SA) for 32 weeks. No body and liver weight changes were evident in any group. Quantitative values for small GST-P+ foci were increased in both sexes of rats exposed to BBN but were not modified by additional SA treatment. Thus, it was confirmed that the selective bladder carcinogen BBN also acts as a liver carcinogen. These results, from the quantitative analysis of small GST-P+ foci as end point marker lesions, indicate that the liver tumor modifying potential of test chemicals can be evaluated in rats by using an initiation/promotion protocol for urinary bladder carcinogenesis.

Animals↗

PubMed1999

Effects of uracil calculi on cell growth and apoptosis in the BBN-initiated Wistar rat urinary bladder mucosa.

The different potential of initiated and non-initiated urinary bladder mucosa (UBM) to develop neoplasia was quantitatively evaluated in the male Wistar rat. Initiation of carcinogenesis was accomplished with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). Stimuli for cell proliferation and apoptosis were obtained by exposure followed by withdrawal of 3% Uracil in the diet. The proliferation index (PI) was estimated in UBM immunostained for the proliferating nuclear cell antigen (PCNA). The apoptotic index (AI) and the density of papillary/nodular hyperplasia (PNH) were estimated in hematoxilin-eosin stained sections. PNH was the main proliferative response to the mechanical irritation by uracil, irrespective of previous initiation with BBN. Uracil exposure induced higher PI and PNH density in the initiated rats. After uracil withdrawal, there was a significant increase of the AI in both uracil-treated groups, which correlated well to the respective PNH density. However, at the end of the experiment, PNH incidence and density were significantly higher in the BBN-initiated mucosa, which also presented 18% incidence of papillomas and 27% of carcinomas. Therefore, under prolonged uracil calculi trauma, the UBM of BBN-initiated Wistar rats gives rise to epithelial proliferative lesions that progress to neoplasia through acquired resistance to apoptosis.

Animals↗

PubMed1981

The cellular features of developing carcinoma in murine urinary bladder.

Bladder cancer often results from a widespread reaction of urothelial cells to carcinogenic stimuli. Although developing carcinoma is widely considered to progress through various grades of epithelial atypia, well-controlled prospective studies detailing the morphologic features of these lesions at the cellular level have not appeared in the literature. This study was designed to document the cellular features of developing urothelial carcinoma in experimental animals using the BHBN model system. Developing lesions were monitored by periodic collection of urine and tissue. The specimens were coded and examined by cytology and histology using multiple discriminators. The morphologic changes in the treated bladders were statistically different from those in control tissue. They could be divided into three stages: 1) The earliest abnormalities were an increase in the number of cell layers, loss of polarity, and slight crowding of nuclei in the tissue sections. Among the cellular features, there were increased nuclear size and sharply angulated indentations (notches) in the nuclear borders. A few nuclei exhibited a finely granular pattern, but dusty chromatin predominated. 2) In the intermediate stage, nuclear crowding became more prominent, and there were numerous areas with finely granular, regularly distributed chromatin. A few nucleoli were identified. Mitoses were prominent in the tissue sections. 3) In the late stage, as papillary tumors developed elsewhere, the urothelium of the flat areas changed significantly. Nuclear crowding and notching remained constant but were overshadowed by the appearance of nucleoli and irregularly distributed chromatin. The pattern was finely granular in some cases but coarsely granular in most. Nuclear size decreased markedly as the cells became smaller and more numerous. Cytologically, it was not possible to distinguish these cells from neoplastic cells emanating from the papillary areas. This experimental study tends to confirm deductions made from clinical material that urothelial carcinoma develops through an orderly sequence of morphologic severity. It further indicates that invasive carcinoma can arise from neoplastic cells that neither occupy the full thickness of the epithelium nor represent lateral migration from an adjacent full thickness lesion. The detailed cellular features documented can be used to identify atypical cells in correlative cytologic preparations. Studies such as this could provide an experimental basis for future evaluations of the cytologic characteristics of human urothelial atypia.

Animals↗

PubMed1984

Effects of intravesical instillation of antitumor chemotherapeutic agents on bladder carcinogenesis in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The effects of intravesical instillation of Adriamycin (doxorubicin) (ADR), and mitomycin C (MMC), as inhibitors of development of rat bladder tumors, were examined in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Intravesical instillation of ADR or MMC once a week for 12 weeks into rats pretreated with BBN for 4 weeks markedly enhanced development of bladder tumors. That is, one week after the end of intravesical instillation of these compounds the incidence of papillary or nodular hyperplasias, namely preneoplastic lesions, was significantly increased, and at the end of the experiment the incidence of not only papillary or nodular hyperplasias but also of papillomas and cancers was significantly increased. These results indicate that the intravesical instillation of ADR or MMC promotes two-stage bladder carcinogenesis in rats.

Animals↗

PubMed1987

Induction of high-grade, high-stage carcinomas in the rat urinary bladder.

The hypothesis that biologic aggressiveness of bladder cancer is determined by carcinogen dose was tested using heterotopically transplanted rat urinary bladders (HTBs). Young male Fischer rats, which were recipients of normal bladders, were divided into three groups; the first group received 0.5 mg of N-methyl-N-nitrosourea (MNU) into HTBs for six doses, a second, 0.05 mg for six doses and the third, 1 mg for three doses. Separately, a group of animals received bladders from rats treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) in drinking water for 4 weeks; the transplanted bladders then were treated with 0.5 mg of MNU for six doses. Treatment with the larger dose of MNU resulted in a significant increase in tumor incidence and frequency of invasive carcinomas. The combination carcinogen treatment induced more invasive carcinomas than the single treatment. The data suggest that deeply invasive carcinomas may develop in two ways: the first is by emergence of a more anaplastic cell population within a pre-existing noninvasive carcinoma and the second is by the de novo development of an invasive carcinoma directly from a severely dysplastic urothelium, which is acceptable as carcinoma in situ. Squamous differentiation was characteristic of deeply invasive carcinomas. The dose of carcinogen(s) is a determinant of aggressiveness of bladder carcinomas.

Animals↗

PubMed1991

Stimulatory effects of growth hormone on rat bladder carcinogenesis.

The authors investigated the influences of recombinant human growth hormone (rh-GH) on rat urinary bladder carcinogenesis induced with N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Rats belonging to the control group (Group I, n = 19) were given 0.05% BBN in drinking water for 9 weeks, and the bladder was excised on the 22nd week after the initiation of BBN administration and inspected. All animals developed visible tumors in the bladder. The mean number of tumors per bladder was 11.26 +/- 5.21, and the mean total volume of tumors per bladder was 126.1 +/- 212.7 microliters. In all but one of the experimental groups (Group V) and in the control group, all animals developed visible tumors in the bladder. When 0.5 units of rh-GH was injected subcutaneously once a week from the week 1 through the week 6 (Group II; n = 20), the mean number of tumors and mean total volume of the tumors were 12.15 +/- 6.59 and 206.6 +/- 318.0 microliters, respectively. When the administration period of rh-GH was changed to between week 7 through the week 12 (Group III; n = 19), the mean number of tumors and mean total volume of the tumors were 16.95 +/- 7.07 and 204.5 +/- 317.7 microliters, respectively. When rh-GH was administered from the week 13 through the week 18 (Group IV; n = 19), the respective values were 16.79 +/- 10.75 and 213.4 +/- 274.6 microliters. In Group V (n = 19), which received only rh-GH from week 1 through the week 6, no tumors were detected. There were statistically significant differences in the mean tumor numbers between Groups I and III, Groups I and IV, and Groups II and III. The mean volume of individual tumor was the greatest in Group II, although the differences were not statistically significant in comparison with the other groups. Histologically, all tumors were transitional cell carcinoma in every group. There were no statistically significant differences in distributions of tumor stage and tumor grade between any groups. These findings suggest that rh-GH enhances the promotion of carcinogenesis of chemically induced rat urinary bladder cancer. It will be necessary to elucidate whether this effect of rh-GH is expressed by the somatostatin hypothesis of GH action, its direct action, or some other mechanisms.

Animals↗

PubMed1985

Modulation of carcinogenesis in the urinary bladder by retinoids.

Bladder cancer has a 70% recurrence rate within five years and a high associated mortality. It commonly occurs in one or both of two predominant growth/behaviour patterns: either well-differentiated, relatively benign exophytic papillary lesions, or flat, poorly differentiated invasive carcinoma usually arising from carcinoma-in-situ. We have used the F344 rat treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as a model for the papillary disease, and the BBN-treated B6D2F1 mouse for flat, invasive bladder carcinoma. In the rat, carcinogenesis is a multistage process and several retinoids will delay or even halt the development of bladder cancer. Inhibition of carcinogenesis is not complete, but there is a consistent reduction in the time-related incidence of papillomas and carcinomas and a concomitant improvement in the overall differentiation of the urothelium. In the BBN/mouse model, retinoids also have anticarcinogenic activity but interpretation of the results is more complicated. Unlike the F344 rat, the B6D2F1 mouse has a non-uniform response to BBN; not all mice develop bladder cancer even after treatment with very high doses of BBN and in those that do, more than one mechanism of carcinogenesis may be involved. Individual retinoids differ markedly in their ability to modulate bladder carcinogenesis in rodents; the behaviour of one analogue cannot be predicted automatically from data obtained with another. Combined data from rodent trials in this and other laboratories have identified N-(4-hydroxyphenyl)retinamide (HPR) as the most anticarcinogenic retinoid tested so far for the rodent bladder. It is also less toxic in rodents and better tolerated in humans than either 13-cis-retinoic acid or etretinate, two retinoids currently used in dermatological practice. A prophylactic chemopreventive trial of HPR in bladder cancer patients starting in 1985 will be centered on the Middlesex Hospital, London.

Animals↗

PubMed1984

Morphologic changes in rat urothelial cells during carcinogenesis: I. Histologic and cytologic changes.

The methods of either image or flow cytometry applied to developing bladder tumors in rats requires satisfactory cell samples and a system for cell classification that is related to the lesions from which the cells are derived. Seven- to eight-week-old male Fisher 344 rats were fed 0.05% of the carcinogen N-butyl-4-N-hydroxybutylnitrosamine (BBN) in drinking water for 10 wk and then returned to tap water. Animals were killed at 14, 26, 34, 45 and 62 wk after the start of carcinogen feeding. Age-matched untreated animals were controls. Bladders were fixed, embedded, sectioned, and histologically evaluated, or were dissociated with a trypsin/EDTA solution into single cells that were Papanicolaou stained and evaluated for cytopathologic changes. Overnight urines were collected before killing; urine sediments were Papanicolaou stained and evaluated. Histologic features were hyperplasia at 14 wk, followed by slowly progressing papillary transitional cell tumors that eventually led to invasive carcinoma and were similar to those reported for this animal model. Treated animals had cytologic features of repair at 14 and 26 wk and neoplastic features at 45 and 62 wk. Both reparative and neoplastic changes were found at 34 wk. Cells were much more numerous in urines from treated rats (greater than 1,000 per sample) than in urines from controls (less than 1,000 per sample). Although exfoliated cells in urine samples were generally of poor quality, as many as 11% of cells were adequately preserved.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Morphologic changes in rat urothelial cells during carcinogenesis: II. Image cytometry.

Improved early detection of neoplasia by screening of urothelial cells requires an understanding of the features distinguishing normal and neoplastic cell populations. We have begun a program of study based upon a rat model system for the controlled observation of early-stage lesions produced by the carcinogen N-butyl-N-(4-hydroxybutyl)- nitrosamine. Cells dissociated directly from normal and malignant urothelium were characterized by conventional cytopathology techniques and by quantitative microscopy (for nuclear texture and nuclear and cytoplasmic size, shape, and stain content) to derive a comprehensive picture of bladder tumor development. By following the changes that occur in the dissociated urothelial cells we have found that the nuclear area, total nuclear stain, nuclear shape, and the nuclear chromatin change significantly over a 48-wk interval as the lesions progress toward malignancy.

Animals↗

PubMed1984

The use of correspondence analysis in the assessment of morphologic changes during carcinogenesis.

Correspondence analysis is a statistical technique originally developed for the analysis of frequency and contingency tables. It may also be successfully applied to the problem of the assessment of the characteristics of samples of cytological material. The present article describes the use of this formalism on feature data measured on urothelial cells in populations obtained from rats at different time points after exposition to a carcinogenic agent. After the application of correspondence analysis, the projections of the samples corresponding to the different time points onto the plane spanned by the first two factorial axes constitute a trajectory, preserving the time ordering. The locations of the projections of cell samples of untreated animals (controls) with respect to this trajectory suggest that two different processes inducing different morphological changes are at work: Early abnormal samples are characterized by a lower-than-normal value of nuclear stain content, whereas late abnormals are mainly characterized by a higher-than-normal nuclear stain value. It is shown that populations of selected atypical cells show less variation throughout the carcinogenic process than populations of randomly selected cells.

Animals↗

PubMed2006

Effects of ginger (Zingiber officinale Roscoe) on DNA damage and development of urothelial tumors in a mouse bladder carcinogenesis model.

Extracts of the spice ginger (Zingiber officinale Roscoe) are rich in gingerols and shogaols, which exhibit antioxidant, anti-inflammatory, antifungal, antimycobacterial, and anticarcinogenic proprieties. The present study evaluated the chemoprotective effects of a ginger extract on the DNA damage and the development of bladder cancer induced by N-butyl-N-(4-hydroxibutyl) nitrosamine (BBN)/N-methyl-N-nitrosourea (MNU) in male Swiss mice. Groups G1-G3 were given 0.05% BBN in drinking water for 18 weeks and four i.p. injections of 30 mg/kg body weight MNU at 1, 3, 10, and 18 weeks. Group G4 and G5 received only the BBN or MNU treatments, respectively, and groups G6 and G7 were not treated with BBN or MNU. Additionally, Groups G2, G3, and G6 were fed diets containing 1, 2, and 2% ginger extract, respectively, while Groups G1, G4, G5, and G7 were fed basal diet. Samples of peripheral blood were collected during the experiment for genotoxicity analysis; blood collected 4 hr after each MNU dose was used for the analysis of DNA damage with the Comet assay (assay performed on leukocytes from all groups), while reticulocytes collected 24 hr after the last MNU treatment of Groups G5-G7 were used for the micronucleus assay. At the end of the experiment, the urinary bladder was removed, fixed, and prepared for histopathological, cell proliferation, and apoptosis evaluations. Ginger by itself was not genotoxic, and it did not alter the DNA damage levels induced by the BBN/MNU treatment during the course of the exposure. The incidence and multiplicity of simple and nodular hyperplasia and transitional cell carcinoma (TCC) were increased by the BBN/MNU treatment, but dietary ginger had no significant effect on these responses. However, in Group G2 (BBN/MNU/2% ginger-treated group), there was an increased incidence of Grade 2 TCC. The results suggest that ginger extract does not inhibit the development of BBN-induced mouse bladder tumors.

Animals↗