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Biomedical subjects

Y Shirasu

Publications and source records attributed to Y Shirasu.

At least 37 records · Page 2Linked to original sources
PubMed1990

Inhibition of induction of adaptive response by o-vanillin in Escherichia coli B.

Mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were strongly enhanced in the presence of o-vanillin in E. coli B. The enhancement was also observed in uvrA, umuC, recA, polA, or alkB mutants. This effect was lower in an alkA mutant, but was restored in an alkA umuC double mutant. By contrast, the enhancing effect was almost blocked in an ada and ada umuC double mutant. It was necessary to add simultaneously MNNG and o-vanillin to the growth medium. Further investigations were conducted on the induction of ada and umuC genes using ada'-lacZ' and umuC'-lacZ' plasmids. o-Vanillin suppressed the induction of the ada gene by MNNG treatment, but not that of the umuC gene. In fact expression of the umuC gene was induced by lower concentrations of MNNG in the presence of o-vanillin. The results suggest that o-vanillin inhibits induction of the adaptive response, and consequently, the MNNG-induced mutation frequency is increased due to unrepaired O6-methylguanine.

Benzaldehydes↗
PubMed1990

Suppressing effects of vanillin, cinnamaldehyde, and anisaldehyde on chromosome aberrations induced by X-rays in mice.

X-ray-induced chromosome aberrations were suppressed when vanillin, cinnamaldehyde, or p-anisaldehyde was given orally to mice after X-ray irradiation. Chromosome aberrations were monitored by the occurrence of polychromatic erythrocytes with micronuclei in bone marrow cells. The frequency of micronuclei was depressed about 55-60% without toxicity of the test compounds to the bone marrow.

Acrolein↗
PubMed1990

Chronic toxicity and carcinogenicity of methylmercury chloride in B6C3F1 mice.

A 2-year feeding study of methylmercury chloride (MMC: 0, 0.4, 2, or 10 ppm) was conducted in B6C3F1 mice (60 mice of each sex/group) to compare chronic toxicity and carcinogenicity results with those for ICR mice from our previous study in which males of the 10-ppm group showed an increased incidence of renal tumors without any abnormal in-life parameters. In B6C3F1 mice of the 10-ppm group, neurotoxic signs characterized by posterior paralysis were observed in 33 males after 59 weeks and in 3 females after 80 weeks. In males, a marked increase in mortality and a remarkable decrease in body weight gain were observed after 60 weeks. Toxic encephalopathy consisting of neuronal necrosis of the brain and toxic peripheral sensory neuropathy were induced in both sexes in this group. Chronic nephropathy, testicular atrophy, and glandular stomach ulcer increased in incidence in the males; chronic nephropathy also increased in incidence in females. In proliferative lesions, there were significant increases in the incidence of renal adenoma and/or carcinoma (16/60) and tubular cell hyperplasia (14/60) in males of the 10-ppm group, as compared to the control group. The incidence of chronic nephropathy also increased in males of the 2-ppm group. The results of this study indicate that the susceptibility of B6C3F1 mice to renal toxicity and renal carcinogenicity is comparable to that of ICR mice, and B6C3F1 mice are more sensitive to the chronic neurotoxic effects of MMC than are ICR mice.

Animals↗
PubMed1990

Pretreatment of rats with an organophosphorus insecticide, chlorfenvinphos, protects against subsequent challenge with the same compound.

A single oral pretreatment of rats with chlorfenvinphos (CVP) reduced toxicity of the same compound subsequently administered. This protection occurred 8 hr and became maximal 24 hr after the oral pretreatment at a dose of 15 mg/kg (about half of its LD50). The 24-hr pretreatment with CVP increased the LD50 of CVP threefold, but did not change the type of toxic signs and time to death caused by CVP. The CVP pretreatment did not appreciably change the toxicities of the cholinergic agonists, carbachol and oxotremorine, but significantly increased the toxicity of another organophosphate, dichlorvos. Oral treatment of rats with CVP (15 mg/kg) inhibited brain acetylcholinesterase (AChE) activity. This inhibition became maximal at 4 hr (about 20% of control) and lasted more than 24 hr after the administration. Twenty-four hours after oral administration of CVP (15 mg/kg), the second dose (CVP 30 mg/kg, po) was less effective in inhibiting cholinesterase activities of the brain, erythrocyte, and plasma compared with naive rats treated with the same dose. The difference in brain AChE activity between control and CVP pretreatment groups was greater in magnitude than that measured in erythrocytes. CVP concentration in plasma after the oral administration of CVP (30 mg/kg) was decreased by the CVP pretreatment. Area under the concentration vs time curve (AUC) in the CVP-pretreated group was about one-fourth of AUC in the control group. This decrease in the AUC was comparable to the decrease in the toxicity of CVP. Thus, the protection against subsequent CVP challenge may be due to the reduction in the inhibition of brain AChE activity caused by the decrease in plasma CVP concentration.

Acetylcholinesterase↗
PubMed1990

Two-year oral chronic toxicity and carcinogenicity study in rats of diets fumigated with methyl bromide.

A chronic toxicity and carcinogenicity study was conducted by feeding diets containing 80, 200 or 500 ppm total bromine following fumigation with methyl bromide, a diet containing 500 ppm potassium bromide, or a basal diet alone to groups of 60 male and 60 female Fischer (F344) rats for up to 2 yr. Ten males and ten females from each group were killed after wk 52 and 104 for urinalysis, haematology, blood biochemistry and pathology. Rats that were killed in extremis or found dead during the study and all rats that survived to the end of the study were also subjected to pathological examinations. In rats fed the diets fumigated with methyl bromide there were no marked toxic changes, except for a slight depression of body-weight gain from wk 60 onwards in males of the 500-ppm group, and tumour incidence was unaffected. Rats given a diet containing potassium bromide did not show any treatment-related changes. It was concluded that residues of up to 500 ppm total bromine in diets fumigated with methyl bromide are not carcinogenic in F344 rats of either sex and that the maximum no-effect level is 200 ppm (6.77 mg total bromine/kg body weight/day) in males. The maximum no-effect level could not be determined in females.

Animals↗
PubMed1990

Male infertility in the hereditary polydactyly (PD) rat.

In the PD strain of rats, male pd homozygotes never sire, whereas male heterozygotes and female hetero- and homozygotes are fertile. In order to investigate the cause of infertility, pd/pd males were examined for their reproductive ability and gross and histological changes in the reproductive organs. Mating ability of pd/pd males was comparable to that of pd/+ males when a 2 week cohabitation procedure was employed. Cryptorchidism, which is considered to be a cause of infertility, was observed in 63% of the 12 week old pd/pd males. However, this abnormality frequently was observed unilaterally and the incidence of bilateral cryptorchidism was only 13%. Although the relative weights of descended testes and epididymides were comparable between the pd/pd and pd/+ males at 3 and 6 weeks of age, the values at 9 and 12 weeks of age were significantly lower in pd/pd males than in pd/+ males. A marked difference was not noted in relative weight changes of the seminal vesicles and prostate between the pd/pd and pd/+ males. Histological examination revealed defects in spermatogenesis in both descended and undescended testes in pd/pd males. The changes first appeared at 9 weeks of age and included vacuolation of nuclei of spermatocytes and spermatids, degeneration of spermatids, and occasionally multinucleated giant cells in the seminiferous tubules. In accessory sexual organs such as the epididymides, seminal vesicles, and prostate, no histological abnormalities were detected. These findings indicate that the substantial cause of infertility in pd/pd males is a disorder of spermatogenesis through which functionally normal spermatozoa are not produced.

Animals↗
PubMed1989

Anatomical features associated with preaxial duplication (pd): a recessive mutation in the rat.

Preaxial polydactyly of the fore- and hindlimbs was found in Wistar-derived rats in 1978. Genetic analysis indicated that the polydactyly was due to the effects of an autosomal recessive gene (gene symbol; pd). Polydactylous homozygous rats had two or three pollices (six or seven digits) in the forelimbs and one to three preaxial extra digits (six to eight digits) in the hindlimbs. Skeletal examination revealed the presence of the extra carpal, metacarpal, and phalangeal bones that seemed to be complete or incomplete duplication of the navicular, greater multangular, first metacarpal, and phalanges of digit I in the forelimbs. In the hindlimbs, extra tarsal, metatarsal, and phalangeal bones were also observed preaxially. These extra elements seemed to be mirror-image duplications of the talus, navicular, second cuneiform, third cuneiform, cuboid, and metatarsals and phalanges of digits II-V with the absence of the first cuneiform, tibiale, first metatarsal, and phalanges of digit I. In addition, morphological changes were observed in the humerus, radius, and ulna in the forelimbs and femur, tibia, and fibula in the hindlimbs. Especially in the radius and tibia, thickening and bifurcation were found, indicating incomplete duplication of these bones. Based on these findings, the limb anomaly was classified as preaxial carpometacarpal/tarsometatarsal-type polydactyly with incomplete duplication of the radius and tibia. The mutant rats had other associated anomalies such as accessory spleens and cryptorchism. The males are sterile, whereas the females breed normally.

Animals↗
PubMed1989

Enhancing effects of cinoxate and methyl sinapate on the frequencies of sister-chromatid exchanges and chromosome aberrations in cultured mammalian cells.

Sister-chromatid exchanges (SCEs) induced by mitomycin C (MMC), 4-nitroquinoline-1-oxide (4NQO) or UV-light in cultured Chinese hamster ovary cells (CHO K-1 cells) were enhanced by cinoxate (2-ethoxyethyl p-methoxycinnamate) or methyl sinapate (methyl 3,5-dimethoxy 4-hydroxycinnamate). Both substances are cinnamate derivatives and cinoxate is commonly used as a cosmetic UV absorber. Methyl sinapate also increased the frequency of cells with chromosome aberrations in the CHO K-1 cells treated with MMC, 4NQO or UV. These increasing effects of methyl sinapate were critical in the G1 phase of the cell cycle and the decline of the frequencies of UV-induced SCEs and chromosome aberrations during liquid holding was not seen in the presence of methyl sinapate. Both compounds were, however, ineffective in cells treated with X-rays. In cells from a normal human embryo and from a xeroderma pigmentosum (XP) patient, MMC-induced SCEs were also increased by the post-treatment with methyl sinapate. The SCE frequencies in UV-irradiated normal human cells were elevated by methyl sinapate, but no SCE-enhancing effects were observed in UV-irradiated XP cells. Our results suggest that the test substances inhibit DNA excision repair and that the increase in the amount of unrepaired DNA damage might cause the enhancement of induced SCEs and chromosome aberrations.

4-Nitroquinoline-1-oxide↗
PubMed1989

Suppressing effect of tannic acid on the frequencies of mutagen-induced sister-chromatid exchanges in mammalian cells.

The effects of tannic acid (m-galloyl gallic acid) and 7 of its analogues on the frequencies of sister-chromatid exchanges (SCEs) were investigated in cultured Chinese hamster cells. SCEs induced by UV-light or mitomycin C (MMC) were suppressed by post-treatment with tannic acid and 5 of its analogues. These effects were independent of the extension of the cell cycle. The compounds which showed an SCE-suppressing effect have a common structure of 3 neighboring hydroxy or methoxy groups substituted on the phenyl group in benzoic acid or ester. These decreasing effects of tannic acid were observed in the G1 phase but not in the S or G2 phase of the cell cycle and a greater decline of the frequencies of UV-induced SCEs during liquid holding was seen in the presence of tannic acid. However, cells irradiated with X-rays were not influenced by tannic acid. In cells from a xeroderma pigmentosum (XP) patient, a Fanconi's anemia (FA) patient, and a normal human embryo, MMC-induced SCEs were also decreased by post-treatment with tannic acid. Tannic acid reduced the SCE frequencies in UV-irradiated FA and normal human cells but not in UV-irradiated XP cells. Our results suggest that tannic acid modifies DNA-excision repair and that the decrease in the amount of unrepaired DNA damage might cause the reduction of induced SCEs.

Animals↗
PubMed1989

Genetic toxicology of 1,2-dibromo-3-chloropropane (DBCP).

1,2-Dibromo-3-chloropropane (DBCP) is a nematocide, which has been used extensively as a soil fumigant in agriculture. Since sterility was found among male workers involved in the manufacture of DBCP, great concern has been focused on the genetic hazards of DBCP. DBCP gave positive results in many tests such as microbial, in vitro cytogenetics, and Drosophila studies. In mammalian test systems, DBCP caused chromosomal aberrations in the bone marrow cells and dominant-lethal mutations in germ cells in rats. In mice, there were no signs of DBCP-induced heritable mutation in germ cells, although point mutations were detected in somatic cells. The occurrence of Y-chromosomal non-disjunction was indicated in DBCP-exposed male workers by an increased number of sperm containing 2 Y-chromosomes.

Animals↗
PubMed1989

Micronucleus test with procarbazine hydrochloride administered by intraperitoneal injection and oral gavage.

The difference in effect of route of administration of procarbazine hydrochloride (PCZ) in the mouse was investigated in the micronucleus test. PCZ was administered by intraperitoneal injection (i.p.) and oral administration (p.o.) to 2 strains of male mice (MS/Ae and CD-1). On the basis of a small-scale acute toxicity test and a pilot micronucleus test, bone marrow preparations were prepared 24 h after the administration by the i.p. and p.o. routes of 50-400 mg/kg and 200-1600 mg/kg, respectively. The maximum incidence of polychromatic erythrocytes with micronuclei (MNPCEs) was somewhat higher after p.o. treatment in MS/Ae mice and the same with both routes in CD-1 mice. Thus, the clastogenicity of PCZ in mouse bone marrow was revealed by both routes.

Administration, Oral↗
PubMed1989

Modifying effects of components of plant essence on the induction of sister-chromatid exchanges in cultured Chinese hamster ovary cells.

The influence of 21 kinds of components of plant essence on sister-chromatid exchanges (SCEs) induced by mitomycin C was investigated in cultured Chinese hamster CHO K-1 cells. Posttreatment with scopoletin, jasmone, caffeic acid and ferulic acid significantly increased the frequency of SCEs. Further investigation of the SCE-enhancing effect of analogues of caffeic acid and ferulic acid revealed that an alpha,beta-unsaturated carbonyl group may be necessary for SCE-enhancing effects. The influence of caffeic acid and ferulic acid on X-ray- or UV-induced SCEs was also studied. The frequencies of SCEs induced by UV were increased by treatment with these compounds. This increasing effect was observed in the S phase of the cell cycle. On the contrary, X-ray-induced SCEs were reduced by the treatment with these compounds. The decreasing effect was observed in the G1 phase but not in the S or G2 phase. To explain these contradictory results, we assumed that caffeic acid and ferulic acid may modify the repair of DNA strand breaks.

Animals↗
PubMed1989

Epiphyseal lesions of the femur and tibia in rats following oral chronic administration of zinc dimethyldithiocarbamate (ziram).

A 24-month chronic feeding toxicity study with zinc dimethyldithiocarbamate (ziram) was performed on Fischer 344 rats of both sexes (80 animals/sex per group) at dietary levels of 0, 20, 200, or 2000 ppm. Eight animals of either sex from each group were sacrificed after 26, 52 and 78 weeks, and all surviving animals were killed after 104 weeks. Epiphyseal abnormalities in the long bones of the hind legs were observed in both sexes at 2000 ppm. Clinically, 3 male rats showed partial paralysis of the hind legs. At necropsy, marked curvature of the proximal end of the crus which could cause a restricted extension of the tibio-femoral joint was seen in 11 of 34 males killed at terminal sacrifice. While females had neither clinical signs nor gross abnormalities during the study, histopathological examination revealed retarded epiphyseal closure of the proximal end of the tibia in both sexes. Females also showed the epiphyseal lesion at the distal end of the femur. In severely affected rats marked proliferation of epiphyseal cartilaginous tissue was also noted together with the irregular arrangement of chondrocytes. These changes were evident only in aged animals. The incidence of the lesions in all males and females examined in this group was 22/77 (29%) and 13/73 (18%), respectively. The occurrence of the lesions appeared to be caused by impaired regulation of epiphyseal closure which might be related to the treatment with ziram.

Administration, Oral↗
PubMed1989

Enhancement and inhibition of mutation by o-vanillin in Escherichia coli.

2-Hydroxy-3-methoxybenzaldehyde (omicron-vanillin), the antimutagenic effect of which has been reported on mutagenesis induced by 4-nitroquinoline 1-oxide (4NQO) in Escherichia coli WP2s, enhanced N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced mutagenesis in the same strain. A remarkable enhancement of mutagenesis provoked by N-methyl-N-nitrosourea (MNU) was also observed by the addition of omicron-vanillin. No enhancing effect was observed on mutagenesis induced by other mutagens such as methyl methanesulfonate (MMS), dimethylsulfate, N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), N-ethyl-N-nitrosourea (ENU), ethyl methanesulfonate, diethylsulfate, 4NQO and furylfuramide (AF-2). On the contrary, omicron-vanillin greatly suppressed AF-2- and 4NQO-induced mutagenesis and showed a slight suppressing effect against mutagenesis induced by MMS, ENNG and ENU. One possible explanation for the enhancing effect of omicron-vanillin on the mutagenesis induced by MNNG or MNU in E. coli WP2s may be inhibition of an inducible adaptive response. Among 7 derivatives of omicron-vanillin, 2-hydroxy-3-ethoxy-benzaldehyde, omicron-hydroxybenzaldehyde and m-methoxybenzaldehyde showed an enhancing effect on MNNG-induced mutagenesis.

Benzaldehydes↗
PubMed1988

Heritable pulmonary lobation anomaly in the rat.

A new mutant gene which caused fusion of lung lobes was found in the Wistar rat. The genetic analysis revealed an autosomal recessive inheritance and the mutant gene was named fused pulmonary lobes (gene symbol: fpl). The right lung of the fpl/fpl homozygotes had fused lobes of varying degrees. The fpl/fpl homozygotes were semilethal at the neonatal stage and had externally visible associated malformations such as malocclusion of incisors, eyelid anomalies, and digit abnormalities in the fore- and hindlimbs with different incidences. These traits were considered to be caused by the pleiotropic effects of the fpl gene.

Abnormalities, Multiple↗
PubMed1988

Post-replication repair and recombination in uvrA umuC strains of Escherichia coli are enhanced by vanillin, an antimutagenic compound.

Effects of vanillin on UV killing of umuC mutant strains of E. coli were investigated in order to analyze the antimutagenic role of vanillin in mutagenesis. UV-irradiated uvrA umuC cells showed higher survival when plated on medium containing vanillin rather than medium without vanillin. This increased survival associated with exposure to vanillin was observed more clearly in uvrA umuC lexA(Ind-) and uvrA umuC recF strains. However, the effect was inhibited by additional recB recC mutations and completely blocked by an additional recA mutation. As far as tested the increased survival of UV-treated cells by vanillin was dependent on a capacity for genetic recombination. The effect of vanillin on recombination frequency between 2 plasmid DNA, pATH4 (Cmr Tcs) and pBMX7 (Apr Tcs), in a uvrA umuC background was investigated. A significantly higher frequency of plasmid recombination was observed when vanillin was present in the culture medium. These findings suggest that the antimutagenic effect of vanillin is the result of enhancement of a recA-dependent, error-free, pathway of post-replication repair.

Benzaldehydes↗
PubMed1988

Suppression of mitomycin C-induced micronuclei in mouse bone marrow cells by post-treatment with vanillin.

Induction of micronuclei by mitomycin C (MMC) in mouse bone marrow cells was suppressed by post-treatment with vanillin, a component of vanilla essence flavour. Vanillin was given orally to mice 7.5 h after intraperitoneal injection of 2 mg/kg MMC. Post-treatment with vanillin at 500 mg/kg caused about 50% decrease in the frequency of micronucleated polychromatic erythrocytes (MN-PCEs). The effect of vanillin administration on the time-course of formation of MN-PCEs was also investigated. The suppressing effect was not due to a delay in the formation of MN-PCEs by the cytotoxic action of vanillin. Vanillin acts as an anticlastogenic factor in vivo.

Animals↗