Biomedical subjects

F Furukawa

Publications and source records attributed to F Furukawa.

At least 55 records · Page 3Linked to original sources

PubMed1999

Effects of Selaginella tamariscina on in vitro tumor cell growth, p53 expression, G1 arrest and in vivo gastric cell proliferation.

Selaginella tamariscina, an oriental medicinal plant, was extracted using water and several organic solvents, and each fraction was assayed for its tumoricidal effects with 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT). Influences on expression of p53 tumor suppressor gene and induction of G1 arrest in the cell cycle were analyzed by Northern blotting and flow cytometry, respectively. The modifying effects of pulverized Selaginella tamariscina on cell turnover in the stomach were also investigated in rats given 150 mg/kg of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by gavage and then fed a diet containing 5, 1 or 0% Selaginella tamariscina. Fractions I-V showed significant tumoricidal effects against cultured human leukemia cells whereas these fractions did not affect normal human lymphocytes. Among the effective fractions, the water-extracted fraction (V) efficiently increased p53 gene expression and induced G1 arrest. The 1% Selaginella tamariscina feeding caused a significant reduction (P < 0.05) in the proliferating cell nuclear antigen-(PCNA) labeling index of the glandular stomach epithelium as compared with the MNNG-alone group value although 5% Selaginella tamariscina feeding was only associated with a tendency for decrease. These results suggest that Selaginella tamariscina could be a candidate chemopreventive agent against gastric cancer.

Animals↗

PubMed1999

Carcinogenic risk assessment of MeIQx and PhIP in a newborn mouse two-stage tumorigenesis assay.

A newborn mouse two-stage tumorigenesis assay was evaluated as a possible alternative to chronic rodent carcinogenicity bioassays by investigating the carcinogenicity of two major heterocyclic amines, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). One week after birth, Crj:CD-1 mice of both sexes were subcutaneously administered N-nitrosobis(2-oxopropyl)amine (BOP) at a dose of 50 mg/kg as an initiation treatment and starting 2 weeks thereafter they were fed diets supplemented with MeIQx at concentrations of 300, 30, 3 or 0 ppm or PhIP at 200, 50, 10 or 0 ppm for 23 weeks. Animals in all groups predominantly developed tumors of the lung and liver. Pulmonary adenomas and adenocarcinomas were observed in all groups with high incidences, without any significant differences between the groups. MeIQx and PhIP did not influence the multiplicity except in the group given 10 ppm PhIP where it significantly increased the number of pulmonary adenomas (P < 0.05). Similarly, hepatocellular adenomas and carcinomas were found in all groups with high incidences, and again MeIQx and PhIP did not increase their incidences or multiplicities. Although adenomas and carcinomas in the nasal cavity, and acinar cell foci in the pancreas were infrequently found, none of these incidences were increased with the MeIQx or PhIP treatments. These results thus suggest that the tumor-promoting effects of MeIQx or PhIP may be rather weak, if present, as far as this newborn two-stage model is concerned, and the possibility that the dose of BOP was too high to detect the tumor-promoting effects of MeIQx or PhIP by masking them cannot be completely ruled out.

Animals↗

PubMed1999

Effect of cigarette smoke on the mutagenic activation of environmental carcinogens by rodent liver.

In order to assess the effect of cigarette smoke (CS) on metabolic enzymes, male hamsters and rats were exposed for two weeks to smoke produced in a Hamburg type II smoking machine. The livers were then used for Ames liquid incubation and western immunoblot assays. Mutagenic activities of seven heterocyclic amines (HCAs) in Salmonella typhimurium TA98 in the presence of rat or hamster liver S9 were elevated up to 3.7 times above controls (including sham smoke control). Enhancement of mutagenic activities of PhIP and aflatoxin B(1) was observed only in CS-exposed hamster, whereas no significant alteration of mutagenicity was observed with 2-aminofluorene, benzo[a]pyrene, and 3'-hydroxymethyl-N, N-dimethyl-4-aminoazobenzene in strain TA98 or with six N-nitrosodialkylamines in strain TA100. 7,8-Benzoflavone and/or furafylline considerably inhibited the mutagenic activation of IQ and Trp-P-1 in the presence of liver S9 from untreated hamsters and sham smoke- or CS-exposed hamsters and rats, indicating the predominant involvement of hamster cytochrome P450 (CYP) 1A enzymes in the metabolic activation of HCAs. In addition, the data suggest that CS-exposure may selectively induce hepatic CYP1A1/1A2 isoforms. Western immunoblot analyses of liver microsomes using anti-rat CYP antibodies revealed that CS-exposure increased the levels of hamster CYP1A2 (3.9-fold) and rat CYP1A2 (3.0-fold) and CYP1A1, without significant change in the levels of CYP2E1 and CYP2B and 3A isoforms in each species. The presently observed selective induction of HCA activation and CYP isozymes due to CS supports the idea that CS may contribute to enhancing effects on initiation by carcinogens which are metabolically activated by hepatic CYP1A1/1A2. In conjunction with results observed for smokers, the present findings indicate that the hamster is a good animal for studies with CS, and that cigarette smoking in combination with intake of heating protein-rich foods as a life style may markedly contribute to the human carcinogenesis by HCAs.

Amines↗

PubMed1999

Failure of phenethyl isothiocyanate to inhibit hamster tumorigenesis induced by N-nitrosobis(2-oxopropyl)amine when given during the post-initiation phase.

The chemopreventive influence of phenethyl isothiocyanate (PEITC) during the post-initiation stage was investigated in the N-nitrosobis(2-oxopropyl)amine (BOP)-initiated hamster tumorigenesis model. A total of 120 female 5-week-old hamsters were divided into six groups. Animals in groups 1-3, each consisting of 30 hamsters, were injected twice, subcutaneously, with BOP 7 days apart to effect initiation. Starting 1 week after the second BOP injection, hamsters in groups 1 and 2 were fed diets supplemented with 6 micromol/g and 3 micromol/g of PEITC, respectively, for 51 weeks. Animals in group 3 received a basal diet as an initiation positive control. Animals in groups 4-6, each consisting of ten hamsters, were given 6 micromol/g or 3 micromol/g of PEITC alone, or were non-treated, matched negative controls for groups 1-3. At the termination of experimental week 52, the incidences and multiplicities of neoplastic lesions in the target organs including the pancreas, lung, liver and kidney were found to be comparable among the BOP-treated groups. The values for pancreatic adenocarcinomas as well as dysplastic lesions tended to increase although without statistical significance. Taken together with our previous finding that PEITC dramatically inhibited the initiation phase of BOP-induced pancreatic and lung tumorigenesis in hamsters, it can be concluded that PEITC specifically exerts chemopreventive effects only when given concomitantly with the carcinogen.

Adenocarcinoma↗

PubMed1999

Promoting effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone on rat glandular stomach carcinogenesis initiated with N-methyl-N'-nitro-N-nitrosoguanidine.

The modifying effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a mutagenic by-product in chlorinated water, on the development of glandular stomach cancers were investigated in Wistar rats. A total of 120 males, 6 weeks of age, were divided into six groups. After initiation with 100 ppm N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) solution and 5% NaCl diet for 8 weeks, 30 rats each in groups 1-3 were given MX in the drinking water at concentrations of 30, 10, or 0 ppm for the following 57 weeks. Ten animals each in groups 4-6 were administered the MX without prior carcinogen exposure. There were no statistical significant differences in final body weights between the groups. The incidences and multiplicities of adenocarcinomas in the glandular stomachs were significantly higher (P < 0.05) in the initiated 30 ppm MX group than those in the MNNG/NaCl group. The incidences of atypical hyperplasias in the glandular stomachs were also significantly increased (P < 0.05 or 0.01) by the MX treatments. With their multiplicity, the effects were clearly dose dependent. Interestingly, the 30 ppm MX alone itself induced atypical hyperplasias in the pylorus, although the incidences and severity were low. Moreover, MX showed a tendency to enhance the development of intrahepatic cholangiocellular tumors and thyroid follicular cell tumors in the MNNG-treated animals. The results of the present study thus indicate that MX exerts promoting effects when given during the postinitiation phase of two-stage glandular stomach carcinogenesis in rats.

Adenocarcinoma↗

PubMed1999

Suppressive effects of josamycin on the development of altered liver cell foci and chronic nephropathy in a carcinogenicity study.

The carcinogenicity of josamycin was examined in Fischer 344 (F344) rats. Groups of 50 males and 50 females were given the compound in their diet at concentrations of 0 (control), 1.25 or 2.5% for 104-weeks; these dose levels were selected on the basis of the results of a subchronic study, in which animals rather rejected 5% josamycin. All surviving rats were killed at wk 106. A variety of tumours developed in all groups, including the control group, but all the neoplastic lesions were histologically similar to those known to occur spontaneously in this strain of rats, and no statistically significant increase in the incidence of any tumour was found in the treated groups of either sex. Interestingly, the josamycin treatment significantly reduced the development of altered liver cell foci and chronic nephropathy in a dose-dependent manner. Thus, it was concluded that, under the present experimental conditions, josamycin is not carcinogenic in F344 rats.

Animals↗

PubMed1999

Lymphocyte stimulation test with drug-photomodified cells in patients with quinolone photosensitivity.

Quinolone antibacterial agents, known to elicit photosensitive dermatitis as an adverse effect, have both phototoxicity and photoallergenicity. The latter potency is mainly derived from their photohaptenic moiety; quinolones covalently bind to protein and cells upon exposure to ultraviolet A (UVA) light. Our previous study has shown the in vivo and in vitro antigenicity of quinolone-photomodified cells in mice. Here, we examined the presence of sensitized lymphocytes that react with quinolone-photomodified autologous cells in patients with photosensitivity to quinolones. A flow cytometric analysis using a monoclonal antibody specific to quinolone photoadducts demonstrated that peripheral blood mononuclear cells (PBMC) were successfully photomodified with quinolones upon exposure to UVA. PBMC from quinolone-photosensitive patients were cocultured with autologous PBMC photomodified with the causative drug. Modest but significant proliferative responses of responder lymphocytes were found in patients photosensitive to lomefloxacin, fleroxacin, and enoxacin, indicating photoallergic mechanism in these patients. On the other hand, sparfloxacin-photosensitive patients exhibited negative lymphocyte stimulation test, suggesting that its photosensitivity is mainly phototoxic. When UVA-preirradiated quinolones were used as stimulators, only fleroxacin exceptionally stimulated patients' PBMC, indicating its prohaptenic as well as photohaptenic properties. These findings suggest the presence of circulating sensitized T cells in patients with photosensitivity to certain quinolones.

Aged↗

PubMed1999

Modulation of T-lymphocyte proliferation by exogenous natural ceramides and sphingosylphosphorylcholine.

Sphingolipids such as ceramide and sphingosine are abundantly present in the stratum corneum of epidermis. In atopic stratum corneum, sphingosylphosphorylcholine (SPC) is present in association with a reduction in the amount of ceramides. We have previously shown that the cellular kinetics of T cells are affected by exogenous addition of sphingosine and synthetic ceramides, raising the possibility that sphingolipids diffusing from the stratum corneum modulate skin-infiltrating T cells. By using two natural ceramides and murine T cells, this study further clarified the conditions under which exogenous ceramides enhance the proliferation of T cells. KLH-specific T cell clones 28-4 and 24-2 proliferated in response to natural ceramides when cultured for 44-48 h in the presence of concanavalin A at 1 microg per ml. Elongation of culture periods adversely inhibited the T cell proliferation, suggesting the existence of an optimal exposure time. Augmentation of DNA synthesis by natural ceramides was more pronounced in tumor necrosis factor alpha (TNFalpha)-sensitive 28-4 cells than in less sensitive 24-2 cells, and TNFalpha-induced proliferation of 28-4 cells was suppressed by the concomitant addition of natural ceramides. Similar to ceramides, SPC augmented the proliferation of resting spleen cells. Our study suggests that ceramide modulation of T cell proliferation depends on the TNFalpha sensitivity and activation level of T cells and that SPC also has a mitogenic potential for T cells.

Animals↗

PubMed1999

Keratinocytes from patients with lupus erythematosus show enhanced cytotoxicity to ultraviolet radiation and to antibody-mediated cytotoxicity.

Keratinocyte cytotoxicity is an important component of the immunopathology of photosensitive lupus erythematosus, and antibody-dependent cell-mediated cytotoxicity (ADCC) has been shown to be an important mechanism by which autoantibodies, especially those specific for SS-A/Ro, can induce keratinocyte damage in models of photosensitive lupus. We provide further evidence that keratinocytes from patients with photosensitive lupus show significantly greater ultraviolet radiation (UVR)-induced cytotoxicity, and that ADCC of these targets is especially enhanced by autologous patient's serum or by anti-SS-A/Ro+ sera. Keratinocytes from normal uninvolved skin of 29 patients with cutaneous lupus erythematosus (LE) were grown in cell culture and tested as targets in cytotoxicity experiments in vitro. Cultured keratinocytes from patients with systemic lupus erythematosus (SLE) and subacute cutaneous lupus erythematosus (SCLE) showed significantly greater cytotoxicity following UVR treatment than did keratinocytes from normal adult controls or from neonatal foreskins (P < 0.01). The same cultures also showed greater UVR-induced binding of IgG from fractionated anti-SS-A/Ro+ preparations. ADCC experiments were also performed using keratinocytes cultured from patients with SLE, SCLE, discoid lupus erythematosus (DLE), and normal controls. When keratinocytes were incubated in autologous serum plus a standard mononuclear cell effector population, the percentage of ADCC observed was significantly greater in cultures containing keratinocytes and sera from the SLE and SCLE patients (P < 0.001). When cultured keratinocytes were added to different IgG antibody probes, plus standard mononuclear effector populations, greater ADCC was seen using the anti-SS-A/Ro probe and keratinocytes from patients with SLE or SCLE. With normal human neonatal keratinocyte targets, the anti-SS-A/Ro probe induced greater ADCC than that seen with anti-ssDNA or normal human serum. We have shown that keratinocytes from patients with some forms of lupus erythematosus (SLE and SCLE) show greater cytotoxicity in vitro when irradiated with UVR, and greater susceptibility to ADCC whether the antibody source is their own serum or an anti-SS-A/Ro probe.

Adult↗

PubMed1999

Treatment of T lymphocytes with 8-methoxypsoralen plus ultraviolet A induces transient but biologically active Th1-skewing cytokine production.

8-Methoxypsoralen plus ultraviolet A light is suggested to shift T lymphocytes from Th2 to Th1 cells. To clarify this issue, we examined the effects of 8-methoxypsoralen/ultraviolet A on the expression/production of cytokines in peripheral blood mononuclear cells from normal subjects and a Sézary syndrome patient. 8-Methoxypsoralen/ultraviolet A augmented the expression of mRNAs for interferon-gamma and interleukin-2 and reduced those for interleukin-4 and interleukin-10. It seems that this enhancement of Th1 cytokines is caused by increment of cytokine production by Th1 cells but not by conversion of Th2 cells to produce Th1 cytokines. The number of interferon-gamma-secreting lymphocytes was markedly increased in 8-methoxypsoralen/ultraviolet A-treated peripheral blood mononuclear cells 20 h after treatment, whereas that of Th2 cytokine-producing cells was decreased. Accordingly, the amount of interferon-gamma was elevated in culture supernatants from 8-methoxypsoralen-phototreated peripheral blood mononuclear cells, whereas interleukin-4 was significantly reduced. This enhanced production of interferon-gamma, however, was found only until 3 d after 8-methoxypsoralen phototreatment and was declined by 5 d after treatment. Finally, 8-methoxypsoralen/ultraviolet A treatment of T cells regulated their ability to induce keratinocyte CD54 expression. Our results show that 8-methoxypsoralen/ultraviolet A has a transient but biologically active Th1-skewing action in human T cells, suggesting that 8-methoxypsoralen/ultraviolet A exerts a beneficial therapeutic effect on Th2-mediated or Th2-malignant diseases.

Cytokines↗

PubMed1999

Inhibition by beta-carotene of upper respiratory tumorigenesis in hamsters receiving diethylnitrosamine followed by cigarette smoke exposure.

In recent intervention studies, beta-carotene failed to reduce or even increased the incidence of lung cancers in smokers. In the present investigation, the modifying effects of beta-carotene at various doses on the development of upper respiratory tract tumors were investigated in Syrian hamsters treated with diethylnitrosamine (DEN) and cigarette smoke. A total of 120 male 5-week-old hamsters were divided into 4 groups, each consisting of 30 animals. After a single subcutaneous (s.c.) injection of 100 mg/kg DEN, hamsters in groups 1-4 were respectively administered diets supplemented with beta-carotene at doses of 0.5%, 0.05%, 0.005% or 0% during experimental weeks 1 to 13, and simultaneously exposed to cigarette smoke. The duration of cigarette smoke exposure was 9 min twice a day, 5 days a week. Because of a marked reduction of body weight in group 1, the highest dose of beta-carotene was changed to 0.25% after 10 days. In all groups, epithelial hyperplasias and/or papillomas were induced in the larynx and trachea. However, the incidence and multiplicity of papillomas in group 1 were significantly (P < 0.05) lower than the group 4 values. Moreover, the beta-carotene treatments significantly (P < 0.05 or 0.01) reduced both the incidence and multiplicity of hyperplasias in a dose-dependent manner. The levels of retinol and beta-carotene in the serum, and the retinol level in the liver, were also elevated with dose dependence. Our results thus indicate that beta-carotene inhibits tumorigenesis, even at the high dose of 0.25%, under the present experimental conditions.

Animals↗

PubMed1999

E- and P-cadherin expression during murine hair follicle morphogenesis and cycling.

The role of adhesion molecules in the control of hair follicle (HF) morphogenesis, regression and cycling is still rather enigmatic. Since the adhesion molecules E- and P-cadherin (Ecad and Pcad) are functionally important, e.g. during embryonic pattern formation, we have studied their expression patterns during neonatal HF morphogenesis and cycling in C57/BL6 mice by immunohistology and semi-quantitative RT-PCR. The expression of both cadherins was strikingly hair cycle-dependent and restricted to distinct anatomical HF compartments. During HF morphogenesis, hair bud keratinocytes displayed strong Ecad and Pcad immunoreactivity (IR). While neonatal epidermis showed Ecad IR in all epidermal layers, Pcad IR was restricted to the basal layer. During later stages of HF morphogenesis and during anagen IV-VI of the adolescent murine hair cycle, the outer root sheath showed strong E- and Pcad IR. Instead, the outermost portion of the hair matrix and the inner root sheath displayed isolated Ecad IR, while the innermost portion of the hair matrix exhibited isolated Pcad IR. During telogen, all epidermal and follicular keratinocytes showed strong Ecad IR. This is in contrast to Pcad, whose IR was stringently restricted to matrix and secondary hair germ keratinocytes which are in closest proximity to the dermal papilla. These findings suggest that isolated or combined E- and/or Pcad expression is involved in follicular pattern formation by segregating HF keratinocytes into functionally distinct subpopulations; most notably, isolated Pcad expression may segregate those hair matrix keratinocytes into one functional epithelial tissue unit, which is particularly susceptible to growth control by dermal papilla-derived morphogens. The next challenge is to define which secreted agents implicated in hair growth control modulate these follicular cadherin expression patterns, and to define how these basic parameters of HF topobiology are altered during common hair growth disorders.

Aging↗

PubMed1999

Antinuclear antibody-keratinocyte interactions in photosensitive cutaneous lupus erythematosus.

Autoimmune diseases are characterized by various circulating autoantibodies, especially antinuclear antibodies (ANA). It has been a long-standing issue as to whether and/or how ANA interact with epidermal cells to produce skin lesions. Of these ANA, the anti-SS-A/Ro antibody is the most closely associated with photosensitivity in patients with systemic lupus erythematosus (SLE) and its subgroups, including subacute cutaneous lupus erythematosus (SCLE) and neonatal lupus erythematosus (NLE). SS-A/Ro antigens are present in the nucleus and cytoplasm, and interestingly, ultraviolet B (UVB) light translocates these antigens to the surface of the cultured keratinocytes. Thus, anti-SS-A/Ro antibodies in the sera can bind to the relevant antigens expressed on the UVB-irradiated keratinocyte surface, and have been speculated to be an important inducer of antibody-dependent keratinocyte damage. This interaction between the anti-SS-A/Ro antibodies and UVB-irradiated keratinocytes may induce the skin lesions through a cytotoxic mechanism. This review will focus on the involvement of antibody-dependent cellular cytotoxicity in the pathogenesis of the skin lesions observed in photosensitive cutaneous lupus erythematosus.

Animals↗

PubMed1999

Influences of long-term administration of 24R, 25-dihydroxyvitamin D3, a vitamin D3 derivative, in rats.

In order to examine the influences by long-term feeding of 24R, 25 dihydroxyvitamin D3[24R, 25(OH)2D3], an active form of vitamin D, Wistar rats (14-week-old, male, 20 rats/group) were fed a powder diet containing 0 or 5 ppm 24R, 25(OH)2D3 for 57 weeks. Final body weights and total food consumption were comparable between the groups. Urinary calcium levels were significantly (p < 0.05 or 0.01) increased by the administration of 24R, 25(OH)2D3 at weeks 3, 22 and 56, although the levels of serum calcium did not differ between the groups at the termination of week 57. In the 24R, 25(OH)2D3 group, weights of the adrenals and femurs were significantly (p < 0.01) increased. Histopathologically, this was found due to thickening of cortical bone in the femurs, and medullary hyperplasia and pheochromocytoma of the adrenals. Immunohistochemically, proliferating cell nuclear antigen (PCNA)-labeling indices for intact adrenal medulla, medullary hyperplasia and pheochromocytoma in the 24R, 25(OH)2D3 group were respectively 1.82 +/- 1.21, 5.88 +/- 4.13 and 16, all higher than that for the adrenal medulla in the control group (0.87 +/- 0.67). These results indicate that 24R, 25(OH)2D3 at a dose with which serum calcium is not chronically increased causes thickening of the cortex of the femur, and development of adrenal proliferative lesions, suggesting that rats may be too sensitive for results to be relevant to human risk assessment.

24,25-Dihydroxyvitamin D 3↗

PubMed1999

Epidermal nuclear CIq deposits in a patient with amyopathic dermatomyositis.

We report a case of amyopathic dermatomyositis, in which C1q deposits on the epidermal nucleus were immunohistologically found as well as Ig deposits at the dermoepidermal junction (DEJ). Direct immunofluorescence (IF) examination of infiltrated erythematous lesions revealed C1q deposits on the epidermal nucleus and fibrinogen at the DEJ, and examination of hyperkeratotic erythematous lesions showed linear deposits of Ig G and Ig A at the DEJ but not in the nuclei of epidermal cells. The authors discuss the direct in vivo interaction between nucleus and immunoreactants in dermatomyositis.

Aged↗

PubMed1999

[A 13-week subchronic toxicity study of D-xylose in F344 rats].

A 13-week subchronic toxicity study of D-xylose was performed in male and female F344 rats at dose levels of 0%, 0.2%, 0.6%, 1.7%, and 5% D-xylose in the CRF-1 powder diet to determine the maximum tolerable dose (MTD) for subsequent investigation of carcinogenicity. Rats were randomly allocated to 5 groups each consisting of 10 males and 10 females. Rats were randomly allocated to 5 groups each consisting of 10 males and 10 females. No treated groups showed changes in body weight gain or food intake, and all animals survived until the end of the experiment. Hematological examination revealed significant increases in RBC, Hb, and Ht in the male groups treated with 0.6% and 5% concentrations, whereas these values decreased significantly in all of the female groups treated with D-xylose. However, no clear dose-response effect was observed in the hematological data in either males or females given D-xylose. Serum biochemistry studies revealed decreases in AsT in the 0.2% and 5% D-xylose group male and 0.2%, 1.7%, and 5% group female, compared to the control value. However, the changes were not considered specific because of the lack of any clear dose-response effect. In addition, no histopathological changes indicating obvious toxicity of D-xylose were observed in the livers of either sex treated with D-xylose. Based on these data, the MTD of D-xylose in F344 rats of both sexes is judged to be 5% or more in the diet.

Administration, Oral↗

PubMed1999

[A 90-day subchronic oral toxicity study of Bacillus subtilis gum in F344 rats].

A 90-day subchronic toxicity study of Bacillus subtilis gum was performed in both sexes of F344 rats by feeding of CRF-1 pellet diet containing 0%, 0.18%, 0.55%, 1.66% and 5%. Rats were randomly allocated to 5 groups, each consisting of 10 males and females. No animals died during the administration period and no differences in body weights and food intakes were found among groups of either sex. Kidney weight was significantly increased in both sexes in the groups given concentrations of 1.66% or more. However, the increases of kidney weight were slight in themselves and other data on serum biochemistry and histopathology did not show any apparent toxicological signs including renal toxicity. These findings indicate that the treatment of Bacillus subtilis gum in the diet for 90 days does not exert serious toxicity in rats even at the highest dose.

Animals↗

PubMed1999

[A 13-week subchronic oral toxicity study of orange color in F344 rats].

A 13-week subchronic toxicity study of orange color was performed in both sexes of F344 rats by feeding them a CRF-1 powder diet containing 0%, 0.18%, 0.55%, 1.66%, and 5% concentrations of the substance. No animals died during the administration period, and no changes in body weight or food intake were found in any of the dosage groups. There were significant increases in serum cholesterol in males given 1.66% or higher concentrations of orange color and in females given 0.55% or higher concentrations, and significant increases in alkaline phosphatase in males given 1.66% or higher concentrations, possibly due to the high-fat composition of the orange color diets. In addition, some hematological, serum biochemical, and histopathological changes were observed in the groups given greater than 0.55% concentrations, but they did not suggest obvious toxicity. These findings indicate that under these experimental conditions the no-observed-effect level (NOEL) of orange color in the diet for 13 weeks is 0.18% and the no-observed-adverse-effect level (NOAEL) is 5%.

Administration, Oral↗