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C Nishigori

Publications and source records attributed to C Nishigori.

At least 55 records · Page 3Linked to original sources
PubMed1993

Activation of c-mos oncogene by integration of an endogenous long terminal repeat element during transfection of genomic DNA from mouse skin tumor cells.

An activated c-mos oncogene was identified in a transformed clone of golden hamster embryo cells transfected with DNA extracted from cells cultured from a UV-induced mouse skin tumor. Southern blot hybridization with a v-mos oncogene probe showed that the mos oncogene was amplified in the primary and secondary transformed cells but not in the original tumor cells. Expression of the mos oncogene was very high in the primary and secondary transformants, but mos mRNA was undetectable in the original tumor cells. A genomic DNA fragment containing the activated mos oncogene was cloned and sequenced. The upstream mouse sequence of the mos oncogene, which functions as the transcription terminator, was lost and replaced by a mouse endogenous long terminal repeat (LTR) element that provides the promoter sequence, resulting in high expression of the gene. The rearrangement apparently occurred during transfection, since the polymerase chain reaction (PCR) product encompassing the junction region was present in the primary and secondary transformants but not in the original tumor cells. The LTR element is likely to have been amplified during the skin tumor development caused by UV irradiation. Southern blot hybridization showed that the copy number of LTR in the tumor cells was significantly higher than that in normal skin cells. The amplification of the LTR in the cells may have increased the chance of recombination between the LTR and c-mos gene during the DNA transfection.

Animals↗
PubMed1992

Infrequent mutation of the ras genes in skin tumors of xeroderma pigmentosum patients in Japan.

By using PCR amplification and oligonucleotide mismatch hybridization, base-substitution mutations of the ras genes in 26 skin tumors of Japanese xeroderma pigmentosum (XP) patients were studied. Thin sections of tumor tissues which were fixed and embedded in paraffin blocks were used in this study. After analyzing codons 12, 13 and 61 of the H-, K- and N-ras genes by using 66 oligomer probes, we detected only one mutation of the K-ras gene at codon 61 in one tumor sample. All the other tumors were therefore considered not to have a mutation in the ras genes. These results suggest that mutations of the ras genes are not particularly associated with skin tumors of Japanese XP patients.

Base Sequence↗
PubMed1992

Amyloidosis cutis dyschromica. DNA repair reduction in the cellular response to UV light.

BACKGROUND: Amyloidosis cutis dyschromica, a special type of primary cutaneous amyloidosis, is assumed to be a congenital disorder and sun exposure is thought to be the major causal factor. Herein we report a case of this rare disease and DNA repair characteristics of UV damages in the fibroblasts derived from the patient. OBSERVATIONS: A 24-year-old Japanese woman showed hyperpigmented and hypopigmented xerotic lesions in sun-exposed skin since she was 10 years old; deposits of amyloid material were detected in the papillary dermis. The fibroblasts were hypersensitive to UV-B, but not so sensitive to UV-C. Unscheduled DNA synthesis of the patient's cells after UV-C exposure was lower than that of normal cells at 3 hours and both reached the same level at 6 hours. After UV-B exposure, unscheduled DNA synthesis of the patient's cells was lower than that of normal cells at least until 6 hours after UV exposure. CONCLUSION: Although the origin of amyloidosis cutis dyschromica is unknown, hypersensitivity to UV-B with possible DNA repair defects is suggested to be the cause of this disease.

Adult↗
PubMed1992

O6-alkylguanine-DNA alkyltransferase activity in human malignant melanoma.

O6-alkylguanine has been known to be the major lesion in DNA for the cytotoxicity of alkylating agents and it is repaired by O6-Alkylguanine-DNA alkyltransferase (O6-AGT). To examine the relation of O6-AGT to the clinical characteristics in malignant melanoma (MM), O6-AGT activity in 13 human MM tissues was measured. The activity in tumor tissues varied widely from 0 to 0.11 pmol/mg protein. The activity in normal skin tissues was lower and less variable than in the tumors. The activity was not related to the tumor size or clinical stage of melanomas, but it was higher in tumors after chemotherapy with alkylating agents than in those without chemotherapy. In metastatic tissues, in primary tumors of the patients with metastases and in tumors of the patients with bad prognosis, the activity was also high. Two of the tumors, having the highest O6-AGT activity, were both transplantable to nude mice. These results suggest two possibilities; melanomas exposed to the alkylating agents may change to have high O6-AGT activity, followed by the resistance to such agents, or O6-AGT in melanomas may be originally diverse. O6-AGT activity in the tumour tissue may represent the effect of alkylating agents and can be used in selecting the methods of therapy.

Adult↗
PubMed1992

Accelerated appearance of skin tumors in hairless mice by repeated UV irradiation with initial intense exposure and characterization of the tumors.

Skin tumors were produced on the back of hairless mice, HOS (HR/De), by exposure to ultraviolet B light (UVB, 290-320 nm) with 4 different protocols. The first tumors appeared earlier (in 10 weeks in group I and 7 weeks in group III) when initial intense exposure was given, followed by repeated lower-level exposures, than when the mice were exposed to the repeated UV only (in 16 weeks both in group II and group IV). All mice developed skin tumors earlier in the groups given the repeated UV exposures three times a week than in the groups given the exposures twice a week. Most of the skin tumors produced by the UVB exposure were histologically malignant, being transplantable to nude mice, and the cultured cells grown from the tumors were capable of producing tumors when injected into nude mice. The accelerated development of skin tumors by initial intense exposure and short intervals of repeated exposure observed in this study may have implications for humans who expose themselves to intense sunbathing and UV tanning (burning) by fluorescent sun lamps.

Animals↗
PubMed1992

A case of xeroderma pigmentosum group A diagnosed with a polymerase chain reaction (PCR) technique. Usefulness of PCR in the detection of point mutation in a patient with a hereditary disease.

BACKGROUND: The gene responsible for the xeroderma pigmentosum (XP) group A gene was recently identified and isolated. Preliminary study with fibroblasts from patients with XP group A revealed that most of the Japanese patients with XP group A have a point mutation at the 3' splice acceptor site of intron 3. This mutation site in the XP group A-complementing gene can be recognized by a restriction enzyme, AlwNI. This article describes the usefulness of the polymerase chain reaction diagnosis on XP group A. OBSERVATIONS: We tried a polymerase chain reaction diagnosis on genomic DNA from a sporadic case of XP group A and this child's parents. AlwNI restriction fragment length polymorphism of the polymerase chain reaction product showed three bands for his father's and mother's DNA, one corresponding to normal and two corresponding to a point-mutated gene, respectively. A DNA sample from our patient showed two fragments indicating that only he has the mutated gene. CONCLUSIONS: This study demonstrated that we can know that this patient has group A XP without a complementation test that needs a lot of time. Moreover, our study revealed that we can detect the hidden mutated XP group A-complementing gene in the pedigree in which there is no patient with XP. Furthermore, it may be available soon for prenatal diagnosis.

Amino Acid Sequence↗
PubMed1991

Analysis of N-methyl-N-nitrosourea-induced mutations in a shuttle vector plasmid propagated in mouse O6-methylguanine-DNA methyltransferase-deficient cells in comparison with proficient cells.

A shuttle vector plasmid, pYZ289, was constructed from the pZ189 plasmid and polyoma virus DNA. The plasmid contains a supF gene as a marker of mutation and can replicate in both Escherichia coli and mouse cells. The pYZ289 plasmids treated with N-methyl-N-nitrosourea were passed through mouse cells originating from skin tumors, which are either proficient (HL18) or deficient (HL8) in O6-methylguanine-DNA methyltransferase activity, and mutations in the supF gene were analyzed. In the repair-deficient HL8 cells, N-methyl-N-nitrosourea-treated pYZ289 showed lower plasmid survival and higher mutation frequency than in the repair-proficient HL18 cells. DNA sequence analysis in the mutated supF gene revealed that most mutations occurred in G:C base pairs (86% for HL8, 76% for HL18), and the frequency of G:C----A:T transition was higher in HL8 cells (69%) than in HL18 cells (31%). G:C----T:A transversions occurred more frequently in HL18 cells (31%) than in HL8 cells (12%). Mutations occurred frequently at the base pair positions of 123 and 159 of supF gene in HL18 cells and at 169 in HL8 cells. Analysis of the bases neighboring the mutations appeared to be related to the mutability of the base pairs with the sequence of 5'-purine-G-G-3' being the most frequently mutated. These results show that the new pYZ289 plasmid is useful for the analysis of mutations and that a deficiency in O6-methylguanine-DNA methyltransferase enhances the N-methyl-N-nitrosourea-induced mutation with significant specificity.

Animals↗
PubMed1991

Altered O6-alkylguanine-DNA alkyltransferase activity in cell strains originating from mouse skin tumors induced by UV irradiation.

O6-Alkylguanine-DNA alkyltransferase (AGT) activity was assayed in the extracts of 47 cell strains originating from mouse skin tumors induced by UV irradiation. They were also examined for the sensitivity to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride by colony formation. The AGT activity (fmol/mg protein) of the tumor cell strains varied widely and the mean +/- SE was 72.5 +/- 9.37, while the AGT activity of the nontumor cell strains was 134 +/- 17. Among 47 strains, 6 strains showed extremely low or no AGT activity, about 5 fmol/mg protein or less, and were hypersensitive to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride. Long-term culture of the tumor cells did not change the AGT activity except in some strains which might have had coexisting normal cells in the population in early passages. All strains showed similar UV sensitivity regardless of AGT activity. This is the first report which demonstrates that about 13% of newly induced tumor cell strains are deficient in AGT activity similar to Mer-/Mex- phenotype that was found in approximately 20% of the established human tumor cell strains.

Animals↗
PubMed1991

Reduced DNA repair in progeria cells and effects of gamma-ray irradiation on UV-induced unscheduled DNA synthesis in normal and progeria cells.

A reduction in the amount of UV-induced unscheduled DNA synthesis (UDS), and reduced cell survival and host-cell reactivation against UV exposure in Hutchinson-Gilford progeria syndrome cell strains were shown. UV-induced UDS in 4 progeria cell strains was 33-50% of the normal level. A similar reduction in the UV-induced UDS in normal cells was caused by gamma-ray irradiation to the cells before UV irradiation. The dose of gamma-rays required to cause a reduction in UDS of normal cells to the level of progeria cells was 40 Gy and the reduction was reversible after 2 days. In progeria cells, gamma-ray irradiation further reduced UDS with a lower gamma-ray dose required than in normal cells, and the reduction was also reversible but with less relative recovery than in normal cells. The presence of a 'built-in' defect in progeria cells responsible for the reduced DNA-repair capacity was suggested, and such defect may share a common mechanism with the reduction of UV-induced UDS in normal cells caused by gamma-ray irradiation.

Adolescent↗
PubMed1991

Superoxide dismutase activity of murine ultraviolet radiation-induced fibrosarcoma cell strains.

The average superoxide dismutase (SOD) activity of seven cell strains from mouse skin fibrosarcoma induced by ultraviolet (UV) irradiation was 5.78 +/- 0.81 (mean +/- SE) unit/mg protein, while that of seven normal mouse skin fibroblasts was 5.36 +/- 1.58. Although tumor cells have been previously reported to exhibit reduced SOD activity, the present study demonstrates that there is comparable SOD activity between tumor cells and normal cells of the same tissue origin.

Animals↗
PubMed1991

Xeroderma pigmentosum patients belonging to complementation group F and efficient liquid-holding recovery of ultraviolet damage.

A 73-year-old woman with xeroderma pigmentosum (XP), XP107TO, was assigned to complementation group F. The fibroblast of this patient showed a reduced level (19%) of unscheduled DNA synthesis (UDS) compared with normal cells. XP107TO cells were 2.3 times more hypersensitive to ultraviolet C (UVC) than normal cells and in the same range of other XPF cells. A clinical case report of 2 patients belonging to XP group F is also described; together with these clinical findings, the characteristics of XP group F are discussed. These patients manifested mild clinical symptoms, developing skin cancer in later age, although acute sun sensitivity was observed in early age (usually a few months after birth). Fibroblasts derived from these patients showed a substantially reduced level of UDS, considering its mild clinical features. To analyze the discrepancy of low UDS level and late onset of skin cancer in XPF cells, we examined the UV sensitivity under density-inhibited condition using XPF cells. XP cells belonging to complementation group F showed marked enhancement of UV survival when they were held in a density-inhibited condition for 1-4 d after UV irradiation. The enhancement was also observed in normal and XP group A cells, but the recovery in these cell lines was less than that in XP group F cells. XP group F cells have been shown to possess slow and long-lasting excision repair capacity and this type of repair might be stimulated by holding through time of the repair process within one cell cycle.

Adult↗
PubMed1990

Another mechanism for the defect in type III collagen accumulation in Ehlers-Danlos syndrome type IV: increased intracellular degradation of the procollagen.

The nature of type III collagen was examined in the skin and cultured skin fibroblasts from a patient with Ehlers-Danlos syndrome type IV. Although the culture medium contained a much lower amount of Type III collagen than the controls, the cells contained an apparently normal amount of Type III collagen. The patient's Type III procollagen showed no abnormalities in apparent molecular weight, the peptide length as examined by cyanogen bromide cleavage, the genomic DNA size including its C- and N-propeptide portion, mRNA size, or thermal stability; but a pulse-chase study revealed prolonged retention of the type III collagen in the cells. Degradation of Type III procollagen was induced by cell extracts but did not occur in the extracellular space and was inhibited in intact cells by the addition of ammonium chloride or leupeptin to the culture medium. Fluorescent staining showed a characteristic granular deposition of Type III procollagen in the peripheral region of the cytoplasm but no granular deposition of Type I procollagen. These results offer new insight into the mechanism of the decreased amount of Type III collagen in the tissue of patients with Ehlers-Danlos syndrome type IV.

Ammonium Chloride↗
PubMed1989

Reduced superoxide dismutase activity in xeroderma pigmentosum fibroblasts.

This study was performed in order to assess the possible protective effect of superoxide dismutase (SOD) on ultraviolet (UV) damage in xeroderma pigmentosum (XP) fibroblasts. SOD activity in fibroblasts originating from seven xeroderma pigmentosum (XP) patients was significantly lower than that in normal cells (p less than 0.005). Average SOD activity in XP cells belonging to complementation group A was 3.68 +/- 0.54 (n = 7) and that in normal human cells was 5.79 +/- 1.59 (n = 6). Addition of SOD before and during UV irradiation (UVB and UVC) to the cells caused no change in the amount of unscheduled DNA synthesis and UV survival. A possible involvement of reduced SOD in XP and a possible protective effect by SOD on UV damage is discussed.

Adolescent↗
PubMed1989

Melanoma and other skin cancers in xeroderma pigmentosum patients and mutation in their cells.

Malignant melanomas were found in 15.8% of xeroderma pigmentosum (XP) patients with skin cancer in Japan. When multiple cancers were scored separately depending on the histopathologic types, 12.1% of the skin cancers in XP patients was malignant malignant melanoma. The relative incidence of malignant melanoma in skin cancer in XP patients is similar to that in skin cancer in general (12.6%), reported previously. Most of the malignant melanoma in XP patients developed in skin exposed to sunlight, in contrast to the high incidence of malignant melanoma in general in the unexposed skin of Japanese people. A DNA repair defect of UV damage is strongly suggested to be responsible for the high incidence of skin cancer in XP patients. The onset of malignant melanoma in XP patients was about ten years old, and was as early as those of basal cell carcinoma and squamous cell carcinoma in the patients with very low DNA repair capacities. Among nine genetic complementation groups and a variant type, group A XP cells were found to be extremely hypermutable by ultraviolet light, while group C XP cells were also hypermutable, but at the same level as normal cells when adjusted for survival. Mutagenesis as a possible mechanism of carcinogenesis in XP is supported by these results, but evidence in other cancer-prone hereditary diseases is yet to be obtained.

Adolescent↗
PubMed1987

Sodium butyrate stimulates cellular recovery from UV damage in xeroderma pigmentosum cells belonging to complementation group F.

Possible stimulation of the DNA repair capacity by sodium butyrate in normal and xeroderma pigmentosum (XP) cells was investigated. XP cells belonging to the complementation group F showed considerable stimulation of DNA repair by sodium butyrate in terms of both the amount of unscheduled DNA synthesis (UDS) and the colony-forming ability after UV irradiation. UDS in XP cells belonging to the complementation group A was not enhanced, while normal cells showed slight enhancement, but less than that of XP F cells. In XP A, XP C, and normal cells, sodium butyrate treatment enhanced the killing effect of UV irradiation. The residual repair capacity in XP F cells appeared to be stimulated by sodium butyrate.

Butyrates↗
PubMed1986

A case of xeroderma pigmentosum with clinical appearance of dyschromatosis symmetrica hereditaria.

A 9-year-old boy complained of increased freckling on the extremities since very early infancy. Examination showed mottled pigmentation with areas of depigmentation on the backs of the hands and tops of the feet, and less strikingly on the arms and legs. Scattered, small, pigmented freckles on the face were also noticed. The condition was clinically diagnosed as dyschromatosis symmetrica hereditaria (DSH) at first. Unscheduled DNA synthesis was reduced to 66% of the normal value, however, and an ultraviolet sensitivity test by colony formation on fibroblasts revealed moderate sensitivity. Therefore this case was finally diagnosed as xeroderma pigmentosum. It is necessary to study cellular repair capacity to make a precise diagnosis when the distinction is so difficult.

Child↗
PubMed1986

Penis tuberculides: papulonecrotic tuberculides on the glans penis.

Two cases of penis tuberculides are described. Although this disease once used to be comparatively common in Japan, the number of people affected by the disease has recently decreased as the prevalence of tuberculosis has fallen. However, we can still find a few cases in the Japanese literature every year. Outside Japan, we can hardly find reports of this disease, except for a few cases reported under the title of 'Papulonecrotic tuberculides on the penis' from Northern European countries. In addition to reporting 2 cases, we summarize clinical features of this disease. Racial predisposition or endemic factors may be related to the tuberculides in such a special site.

Antitubercular Agents↗