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Biomedical subjects

A Nishikawa

Publications and source records attributed to A Nishikawa.

At least 73 records · Page 4Linked to original sources
PubMed2000

Developmental regulation of a gene coding for a low-molecular-weight heat shock protein during haustorium formation in the seedlings of a holoparasitic plant, Cuscuta japonica.

Dodder (Cuscuta japonica), a holoparasitic angiosperm, develops haustoria that are essential for parasitism. We have previously demonstrated that in Cuscuta seedlings, haustorial formation could be induced efficiently by cooperative effects of far-red light and tactile stimuli in the absence of any host plant [Tada et al. (1996) Plant Cell Physiol. 37: 1049]. In this study, we performed differential display and isolated several cDNAs that were expressed differentially during haustorium development in the seedlings. Sequence similarities identified one of them as a gene encoding a 17-kDa low-molecular-weight heat shock protein (CJHSP17). Northern blot analysis revealed that CJHSP17 mRNAs constitutively accumulated in the seedlings in the absence of environmental stress, and that the transcripts dramatically decreased to undetectable levels prior to emergence of haustoria upon irradiation with far-red light in the presence of tactile stimuli. When treated with either of the two stimuli, the CJHSP17 transcript levels did not decrease and there was no differentiation of haustoria. Moreover, irradiation of red light immediately after far-red light completely repressed both the decrease of mRNAs and the subsequent formation of haustoria. These observations suggest the involvement of down-regulation of CJHSP17 in haustorium development in Cuscuta seedlings.

Amino Acid Sequence↗
PubMed2000

Comparative study of Staphylococcus aureus isolated from lesional and non-lesional skin of atopic dermatitis patients.

The skin of patients with atopic dermatitis (AD) is often colonized by Staphylococcus aureus, and superantigenic exotoxins produced by the organism are thought to be an important precipitating factor of AD. However, there are few reports comparing the characteristics of S. aureus isolated from the lesional and non-lesional skin of identical AD patients. In this study, therefore, we examined whether the presence of superantigen-producing S. aureus correlates with the formation of eczematous lesion of AD patients. The detection rate of S. aureus on the lesional skin of AD patients was higher than on the non-lesional skin of AD patients. Furthermore, the bacterial cell count of S. aureus on the lesional skin of AD patients was also significantly higher than that of the non-lesional skin of AD patients. However, there was no significant difference between the detection rate of superantigenic exotoxin-producing S. aureus on the lesional and nonlesional skin of AD patients. These results suggest that the number of S. aureus present is more important in the formation of eczematous lesion of AD patients than the presence of superantigenic exotoxin-producing S. aureus strains per se.

Adolescent↗
PubMed2000

Lack of modification by environmental estrogenic compounds of thyroid carcinogenesis in ovariectomized rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN).

The effects of environmental estrogenic compounds, soy isoflavone mixture (SI), genistein (GEN), and nonylphenol (NP), and the possible goitrogen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), on thyroid carcinogenesis were investigated in ovariectomized (OVX) female rats. Five-week-old OVX F344 rats were given a single subcutaneous injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN; 2400 mg / kg, body weight) or vehicle alone. Starting 1 week later, GEN (250 or 25 ppm in diet), SI (400 ppm in diet), NP (250 or 25 ppm in diet), MX (30 ppm, in drinking water), sulfadimethoxine (SDM), a known thyroid tumor-promoter (1000 ppm in drinking water), or beta-estradiol 3-benzoate (EB), a synthetic estrogen (0.5 mg in cholesterol pellet, s.c.) were administered for 12 weeks. SDM and EB were included as positive controls. At sacrifice the major organs including the thyroid, pituitary, liver, kidney, uterus, vagina, brain and pancreas were collected and histopathological observation was performed. Thyroid weights were significantly increased (P < 0. 001) only in the SDM treatment group and pituitary weights were elevated with SDM (P < 0.05) and EB (P < 0.001). Kidney and uterus weights were also significantly increased (P < 0.05) by EB. Histopathologically, proliferative lesions of the thyroid were only observed in the SDM treatment group and of the pituitary in the SDM or EB treatment groups. Renal tubule lesions, uterine squamous metaplasia, vaginal keratinization and telangiectasia of pancreatic islets were also observed with EB. There were no organ weight changes or histopathological lesions in the major organs, including the thyroid, in the GEN, SI, MX or NP treatment groups. Our results thus indicated a lack of modifying effects on thyroid carcinogenesis in female OVX rats, in agreement with our previous finding in males.

Aminoacridines↗
PubMed2000

Renal carcinogenicity of concurrently administered fish meal and sodium nitrite in F344 rats.

The effects of long-term concurrent administration of powdered fish meal and sodium nitrite were examined in F344 rats. A total of 600, 6-week-old rats were divided into 6 male and 6 female groups, each consisting of 50 animals. Rats in groups 1-3 and 7-9 were respectively fed diets supplemented with 64%, 32% and 8% (basal diet) fish meal, and simultaneously given 0.12% sodium nitrite in their drinking water. Groups 4-6 and 10-12 were respectively given 64%, 32% and 8% fish meal and tap water. At the 104th week, all surviving animals were killed and examined histopathologically. Treatment with fish meal dose-dependently increased the incidences and multiplicities of atypical tubules, adenomas and renal cell carcinomas in sodium nitrite-treated males. Females were less susceptible than males for renal tumor induction. In males given the 64% fish meal diet alone, the incidence and multiplicity of atypical tubules were also significantly increased as compared with the 8% fish meal alone case. Nephropathy was apparent in fish meal-treated groups in a clear dose-dependent manner, irrespective of the sodium nitrite treatment, and was more prominent in males than in females. Dimethylnitrosamine was found in the stomach contents after 4-week treatment with 64% fish meal plus 0.12% sodium nitrite, at a level twice that in the 8% fish meal plus 0.12% sodium nitrite group. The results clearly indicate that concurrent administration of fish meal and sodium nitrite induces renal epithelial tumors. Further studies are required to elucidate how nephropathy and nitrosamines produced in stomach contents may contribute to the observed renal tumor induction.

Animals↗
PubMed2000

Inhibitory effects of 1'-acetoxychavicol acetate on N-Nitrosobis(2-oxopropyl)-amine-induced initiation of cholangiocarcinogenesis in Syrian hamsters.

The influence of 1'-acetoxychavicol acetate (ACA) during the initiation stage was investigated in the N-nitrosobis(2-oxopropyl)amine (BOP)-initiated hamster tumorigenesis model. Ninety male 5-week-old hamsters were divided into three groups, each consisting of 30 animals, and s.c. injected with 20 mg / kg of BOP twice with a one-week interval. Groups 1 through 3 were fed diet supplemented with ACA at concentrations of 500, 100 and 0 ppm, respectively, for 3 weeks starting one week before the first carcinogen application. At the termination of experimental week 54, the total incidence and multiplicity of cholangiocellular adenomas and carcinomas in group 1 (17.9% and 0.3 < 0.9) were significantly (P < 0.05 and P < 0.01) decreased as compared to the group 3 values (50.0% and 0.7 < 0.8). The ACA treatments also showed a tendency to reduce the development of preneoplastic lesions in the pancreas, a main target organ of BOP, although this was not statistically significant. Our results thus indicate that ACA exerts an inhibitory effect on BOP-induced cholangiocarcinogenesis in hamsters. Taken together with previous findings of inhibited colon, oral and skin carcinogenesis in rats and mice, they suggest that ACA is a candidate chemopreventive agent with a wide spectrum of activity.

Adenocarcinoma↗
PubMed2000

A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter in endometrial carcinomas.

Recent studies demonstrated that a single guanine insertion polymorphism in a matrix metalloprotease-1 promoter created an Ets binding site and affected the elevation of the transcriptional level of matrix metalloproteinase-1 (MMP-1). Furthermore, in tumor cell lines derived from melanoma and breast cancer, the incidence of the 2G / 2G genotype was significantly higher than that in the normal population. To evaluate the contribution of this polymorphism in endometrial carcinomas, we genotyped 100 endometrial carcinomas and then analyzed immunoexpression of MMP-1 in these carcinomas. We found that endometrial carcinoma patients showed a significantly higher rate of 1G / 2G or 2G / 2G genotype than control individuals, and that tumors containing the 2G allele(a) expressed MMP-1 protein more frequently than those with 1G / 1G genotype. Therefore, the single nucleotide polymorphism at the MMP-1 promoter affected the expression level of the MMP-1 protein, which may result in the association with more aggressive character in endometrial carcinoma. Our result suggests that the presence of 2G polymorphism at the MMP-1 promoter may be one of the risk factors for the development and / or progression of endometrial carcinoma.

Base Sequence↗
PubMed2000

Lack of modifying effects of environmental estrogenic compounds on the development of thyroid proliferative lesions in male rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN).

The modifying effects of various environmental estrogenic compounds on thyroid carcinogenesis were investigated in a rodent two-stage carcinogenesis model. The compounds examined were a soy isoflavone mixture (SI) and genistein (GEN) as phytoestrogens, nonylphenol (NP) as a xenoestrogen, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) as a thyroid carcinogen and sulfadimethoxine (SDM) as a known thyroid tumor promoter. Five-week-old male F344 rats were given a single subcutaneous injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN; 2800 mg / kg, body weight) or the vehicle alone. Starting one week thereafter, GEN (250 or 25 ppm in diet), SI (400 ppm in diet), NP (250 or 25 ppm in diet), MX (30 ppm, in drinking water) or SDM (1000 ppm in drinking water) was administered for 12 weeks. Major organs including the thyroid, pituitary, liver, kidney, testis, brain and pancreas were weighed and histopathological observation was performed. Thyroid weights were significantly increased (P < 0.001) only in the SDM treatment groups, especially with DHPN pretreatment. Kidney weights were slightly increased in the NP or MX treatment groups, albeit without statistical significance. Histopathologically, thyroid proliferative lesions were only observed in the SDM alone or DHPN + SDM group with significant focal hyperplasias, adenomas and adenocarcinomas limited to the combined treatment case. There were no organ weight changes or histopathological lesions in the major organs including the thyroid in the GEN, SI, NP, and MX treatment groups regardless of DHPN pretreatment. Our results thus indicate that the weakly estrogenic compounds GEN, SI and NP and the environmental rat thyroid carcinogen MX do not exert any modifying effects on thyroid carcinogenesis in rats under the present experimental conditions.

Animals↗
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

Structural characterization of chemically derivatized oligosaccharides by nanoflow electrospray ionization mass spectrometry.

Oligosaccharides released from several glycoproteins were derivatized with either 4-aminobenzoic acid 2-(diethylamino)ethyl ester (ABDEAE) (Yoshino, K.; et al. Anal. Chem. 1995, 67, 4028-4031) or 2-aminopyridine. The resulting derivatives were analyzed on a nanoflow electrospray ionization (ESI) quadrupole-inlet time-of-flight mass spectrometer using the low-energy collision-induced dissociation technique. In the MS/MS spectra, the oxonium (b or internal series) and y series ions, which are derived from the multiply charged precursor ions, were predominant and were used for the structural readout. Some oxonium ions that were observed in the low-mass region, but that were not found in the PSD analyses (Mo, W.; et al. Anal. Chem. 1998, 70, 4520-4526), rendered a more detailed structural insight. The oxonium ions at m/z 512.2, which are derived from the fucosylated oligosaccharides of immunoglobulin Y and thyroglobulin, were observed, suggesting that fucosylation had occurred proximal to the outer nonreducing terminus. In addition, the data herein show that structural elucidation can be routinely achieved at a low sample concentration. For the case of ABDEAE derivatives, this can be achieved at the 50 fmol/microL level and with the actual sample consumption at the attomole level using nanoflow ESI MS/MS.

Aminopyridines↗
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

Identification of amino acids that modulate mannose phosphorylation of mouse DNase I, a secretory glycoprotein.

We have reported that bovine DNase I, a secretory glycoprotein, acquires mannose 6-phosphate residues on 12.6% of its Asn-linked oligosaccharides when expressed in COS-1 cells and that the extent of phosphorylation increases to 79.2% when lysines are placed at positions 27 and 74 of the mature protein (Nishikawa, A., Gregory, W. , Frenz, J., Cacia, J., and Kornfeld, S. (1997) J. Biol. Chem. 272, 19408-19412). We now demonstrate that murine DNase I, which contains Lys27 and Lys74, is phosphorylated only 20.9% when expressed in the same COS-1 cell system. This difference is mostly due to the absence of three residues present in bovine DNase I (Tyr54, Lys124, and Ser190) along with the presence of a valine at position 23 that is absent in the bovine species. We show that Val23 inhibits phosphorylation at the Asn18 glycosylation site, whereas Tyr54, Lys124, and Ser190 enhance phosphorylation at the Asn106 glycosylation site. Tyr54 and Ser190 are widely separated from each other and from Asn106 on the surface of DNase I, indicating that residues present over a broad area influence the interaction with UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase, which is responsible for the formation of mannose 6-phosphate residues on lysosomal enzymes.

Amino Acid Sequence↗
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

Endogenous formation and significance of 1,N2-propanodeoxyguanosine adducts.

The detection of 1,N2-propanodeoxyguanosine adducts in the DNA of rodent and human tissues as endogenous lesions has raised important questions regarding the source of their formation and their roles in carcinogenesis. Both in vitro and in vivo studies have generated substantial evidence which supports the involvement of short- and long-chain enals derived from oxidized polyunsaturated fatty acids (PUFAs) in their formation. These studies show that: (1) the cyclic propano adducts are common products from reactions of enals with DNA bases; (2) they are formed specifically from linoleic acid (LA; omega-6) and docosahexaenoic acid (omega-3) under in vitro stimulated lipid peroxidation conditions; (3) the levels of propano adducts are dramatically increased in rat liver DNA upon depletion of glutathione; (4) the adduct levels are increased in the liver DNA of the CCl4-treated rats and the mutant strain of Long Evans rats which are genetically predisposed to increased lipid peroxidation; and (5) adduct levels are significantly higher in older rats than in newborn rats. These studies collectively demonstrate that tissue lipid peroxidation is a main endogenous pathway leading to propano adduction in DNA. The possible contribution from environmental sources, however, cannot be completely excluded. The mutagenicity of enals and the mutations observed in site-specific mutagenesis studies using a model 1,N2-propanodeoxyguanosine adduct suggest that these adducts are potential promutagenic lesions. The increased levels of the propano adducts in the tissue of carcinogen-treated animals also provide suggestive evidence for their roles in carcinogenesis. The involvement of these adducts in tumor promotion is speculated on the basis that oxidative condition in tissues is believed to be associated with this process.

Animals↗
PubMed1999

Effects of protocatechuic acid, S-methylmethanethiosulfonate or 5-hydroxy-4-(2-phenyl-(E)ethenyl)-2(5H)-furanone(KYN-54) on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced pulmonary carcinogenesis in mice.

Modifying effects of dietary exposure of protocatechuic acid (PCA), a natural monophenolic compound, S-methylmethanethiosulfonate (MMTS), an organosulfur compound newly isolated from cauliflower, and 5-hydroxy-4-(2-phenyl-(E)ethenyl)-2(5H)-furanone (KYN-54), a novel retinoidal butenolide compound, on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (10 micromol, [corrected] single i.p. injection)-induced pulmonary carcinogenesis were examined in female A/J mice. Each of the test chemicals was given in diets during initiation or post-initiation phases (PCA, 1000 ppm; MMTS, 100 ppm; KYN-54, 200 ppm). All of these which had been proved to be chemopreventive mainly in digestive-organs carcinogenesis did not exert any preventive effect in this model when the incidence or multiplicity of pulmonary tumors (adenomas) of mice given NNK and the test chemical at the termination of the experiment (4 months) was compared to that of mice exposed to the carcinogen alone. In contrast, the multiplicity of lung tumors of mice receiving KYN-54 during the post-initiation phase was significantly larger than of the animals with NNK alone (P < 0.05), showing that KYN-54 has a promoting effect on pulmonary carcinogenesis in mice. These data indicate an organotropic activity of these compounds and suggest that candidate compounds for cancer chemoprevention need to be carefully examined for effectiveness in multiple organs by different models.

4-Butyrolactone↗
PubMed1999

T3-hydrocortisone synergism on adult-type erythroblast proliferation and T3-mediated apoptosis of larval-type erythroblasts during erythropoietic conversion in Xenopus laevis.

The conversion of an erythropoietic system from larval to adult type in anuran amphibia may possibly come about through cell replacement. The hormonal regulation of apoptosis of larval-type precursor cells and adult-type cell proliferation has yet to be examined in detail. In amphibians, corticoids synergize T3 action during metamorphosis. In the present study, examination was made of the process of larval-to-adult conversion in the liver erythropoietic site of Xenopus laevis, with special attention to how these metamorphic hormones, T3 and corticoid, regulate programmed cell death specific for larval erythroblasts and the proliferation of adult cells. Immunohistochemical analysis of liver sections indicates that the number of larval erythroblasts decreased to less than 50% at the early climax stage (stages 59-60) of metamorphosis. Overall liver morphology greatly changed subsequent to the climax stage from the three-lobe to the two-lobe shape. The addition of T3 (10(-8) M) to premetamorphic tadpoles induced considerable liver morphological change and a 50% decrease in larval-type erythroblasts. These erythroblast decreases seem to take place through the apoptotic process, since double-staining experiments with in situ DNA nick-end labeling (TUNEL) and hemoglobin immunostaining revealed that DNA breakage of nuclei, a well-known feature of apoptosis, occurred specifically in larval erythroblasts during prometamorphosis. Hydrocortisone (HC), which modulates T3 action during metamorphosis, was found not to be a factor in larval cell decrease. But adult erythroblasts increased by 8 times as much through the action of T3 and 32 times as much by the action of T3 plus HC, indicating the important action of T3-HC synergism. It thus follows that the erythropoietic system is converted during metamorphosis effectively by two distinct hormonal mechanisms, T3-HC synergism on adult erythroblast proliferation and T3-mediated programmed death of larval precursor cells.

Animals↗