Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0349506 (photosensitivity)
 4,145 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Photosensitive genodermatoses associated with established defects of DNA repair currently include the autosomal recessive diseases xeroderma pigmentosum (XP), Cockayne's syndrome (CS), trichothiodystrophy (TTD), and Bloom's syndrome (BS). XP is a heterogeneous disorder associated with defective excision repair or daughter strand repair of ultraviolet (UV)-induced DNA damage. It is characterized by cutaneous and ocular abnormalities predominantly on sun-exposed sites and in some cases, neurological features resulting from progressive neuronal loss. Skin involvement includes easy sunburning, pigmentary abnormalities, telangiectasia, dryness, scarring, and susceptibility to multiple benign and malignant neoplasms. In CS, defective repair of actively transcribing DNA is clinically associated with acute photosensitivity, growth retardation, demyelinating neurological abnormalities, and pigmentary retinal degeneration, but without increased cancer susceptibility. TTD is characterized by sulphur-deficient brittle hair, variable growth delay, mental retardation, ichthyosis, and in some cases photosensitivity. Although in some patients there is a deficiency of DNA excision repair identical to that in certain xeroderma pigmentosum patients, no increased cancer risk is present in trichothiodystrophy. In BS, deficient cellular DNA ligase is associated with congenital telangiectasia, photosensitivity, growth retardation, immune deficiency, increased susceptibility to infection, and predominantly internal rather than cutaneous malignancy. Immunological factors may at least determine the varying susceptibility to malignancy of these conditions.
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PMID:DNA repair deficient photodermatoses. 220 44

A case of xeroderma pigmentosum (XP) with neurological disorders is reported. The patient is a 16 year old male who presented a marked photosensitivity from his early infancy. The family history is negative for XP with no consanguinity being observed. He displayed neurological symptoms such as a low IQ and audiological disturbances. He developed six basal cell epitheliomas (BECEs) on his face at age of 14. We tried oral etretinate for 4 years at a initial dosage of 30 mg per day for the possible prevention of new skin cancers. Efficacy of the drug for prevention of cancers has not been confirmed, but evidence is obtained that the drug might prevent the growth of tumors. We also reviewed the chemoprevention of skin cancers with retinoids, in patients with xeroderma pigmentosum.
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PMID:[A case of xeroderma pigmentosum treated by oral etretinate]. 225 7

Trichothiodystrophy (TTD) is an autosomal recessive disorder characterized by brittle hair with reduced sulfur content, ichthyosis, peculiar face, and mental and physical retardation. Some patients are photosensitive. A previous study by Stefanini et al. (Hum. Genet., 74: 107-112, 1986) showed that cells from four photosensitive patients with TTD had a molecular defect in DNA repair, which was not complemented by cells from xeroderma pigmentosum, complementation group D. In a detailed molecular and cellular study of the effects of UV light on cells cultured from three further TTD patients who did not exhibit photosensitivity we have found an array of different responses. In cells from the first patient, survival, excision repair, and DNA and RNA synthesis following UV irradiation were all normal, whereas in cells from the second patient all these responses were similar to those of excision-defective xeroderma pigmentosum (group D) cells. With the third patient, cell survival measured by colony-forming ability was normal following UV irradiation, even though repair synthesis was only 50% of normal and RNA synthesis was severely reduced. The excision-repair defect in these cells was not complemented by other TTD cell strains. These cellular characteristics of patient 3 have not been described previously for any other cell line. The normal survival may be attributed to the finding that the deficiency in excision-repair is confined to early times after irradiation. Our results pose a number of questions about the relationship between the molecular defect in DNA repair and the clinical symptoms of xeroderma pigmentosum and TTD.
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PMID:Trichothiodystrophy, a human DNA repair disorder with heterogeneity in the cellular response to ultraviolet light. 245 32

Xeroderma pigmentosum (XP) is an autosomal recessive human disease, clinically characterized by the early onset of severe photosensitivity of exposed skin to sunlight, a very high incidence of skin cancers and frequent neurological abnormalities. Cells from XP patients are hypersensitive to killing by UV-light, because they have a defect in repair of UV-light induced DNA damage. Genetic complementation analysis by cell fusion has led to the identification of at least ten genetic complementation groups, designated as group A through I, and a variant. However, the genetic basis of the physiological defect of XP has not yet been characterized. For isolation of the gene responsible for XP complementation group A, the pSV2gpt and genomic DNA from a mouse embryo were co-transfected into XP2OSSV group A XP cells. Two primary UV-resistant XP transfectants were isolated from about 1.6 X 10(5) pSV2gpt transformed XP colonies. The pSV2gpt and genomic DNA from the primary transfectants were again co-transfected into XP2OSSV cells, and a secondary UV-resistant XP transfectant was obtained by screening about 4.8 X 10(5) pSV2gpt transformed XP colonies. The secondary transfectant retained fewer mouse repetitive sequences. A mouse gene that complements the defect of XP2OSSV cells was cloned into EMBL3 vectors from the secondary transfectant. Transfections of the cloned DNA also conferred UV-resistance on another group A XP cell line, but not on group C, D, F or G XP cell lines, suggesting that the cloned DNA repair gene is specific for group A XP and may be the mouse counterpart of the group A XP human gene.
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PMID:[DNA repair defect in xeroderma pigmentosum]. 265 Jun 28

Experiments were performed to determine if differences in porphyrin photosensitivity could be observed for cells with varying efficiency in DNA damage repair, as well as for cells which make up components of the vasculature. Photofrin II is undergoing current clinical evaluation for photodynamic therapy of solid tumors, and therefore the retention, dark toxicity, and photosensitizing effects of this drug on human DNA repair-deficient fibroblasts (ataxia telangiectasia and xeroderma pigmentosum) were compared to normal human fibroblasts. In addition, bovine cells of endothelial, smooth muscle, and fibroblast origin were compared for porphyrin retention, toxicity, and photosensitivity. All human fibroblasts exhibited porphyrin-induced dark toxicity, but there were no significant differences in photosensitization or porphyrin retention for any of these cell lines. However, bovine endothelial cells were considerably more photosensitive than smooth muscle or fibroblast cells treated under identical conditions. All bovine cells accumulated similar levels of porphyrin, and therefore the increased sensitivity of the endothelial cells was not due to differences in porphyrin retention. These results provide additional evidence that nuclear damage and/or repair is not a dominant factor in the cytotoxicity induced by porphyrin photosensitization. In addition, these results indicate that endothelial cell photosensitivity may play a role in the vascular damage observed following photodynamic therapy.
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PMID:Differential cell photosensitivity following porphyrin photodynamic therapy. 296 80

Photosensitivity diseases are reviewed. The pathogenesis of photodermatoses is not completely elucidated, especially because the photosensitizing agents are rarely identified. In exogenous photosensitization, the chemical agent (chromophore) is most often identified, reaching the skin either via topical contact or by systemic administration (drugs). Concepts of phototoxicity (photochemical reaction) and photo-allergy (photo-immunologic reaction) explain the clinical aspects. Dermatoses with photosensitivity are divided into three groups: photo-aggravated dermatoses (solar herpes, lupus erythematosus), photosensitivity caused by protective system defect (xeroderma pigmentosum), and photosensitivity caused by metabolic defects (porphyrias, pellagra). Idiopathic photodermatoses (unknown chromophore) are triggered by solar exposure (systemic photo-allergens would serve as mediators): 'benign estival polymorphous light eruption', polymorphous light eruptions, persistent light reactor, solar urticaria.
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PMID:[Photosensitivity in human pathology: mechanisms and clinical aspects]. 309 82

Chediak-Higashi syndrome (CHS) cells have been previously observed to exhibit several of the same characteristics as those of xeroderma pigmentosum (XP) and xeroderma pigmentosum variants. Cultured CHS fibroblasts have been examined for altered responses in both depletion of NAD and elevation of diadenosine-5',5"'-tetraphosphate (Ap4A) following DNA damage since both responses have been reported as altered in XP cells and since Ap4A has been reported as absent from the platelets of CHS patients. Lowering of NAD following UV irradiation occurred in CHS cells in a manner similar to that of control and XP variant cells, but different from that of XP cells. CHS fibroblasts were not found to be deficient in Ap4A and exhibit basal levels very similar to those of control fibroblasts. No change in Ap4A pools were observed which correlated with cell growth, in contrast to previously published reports. Furthermore, while Ap4A levels are not elevated in XP cells, we observe an elevation of Ap4A pools in CHS cells which mimics the elevations observed in control and XP variant cells. We conclude that: (1) CHS cells more closely resemble control or XP variant cells than XP cells with regard to NAD lowering and Ap4A elevation following UV irradiation; (2) the photosensitivity exhibited by CHS cells is not due to general defects in the synthesis of poly(ADP-ribose) from NAD or in Ap4A metabolism; and (3) alteration of Ap4A pool size in CHS fibroblasts is inappropriate as a biochemical marker for CHS.
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PMID:Alterations of NAD and adenylyl dinucleotide metabolism in Chediak-Higashi syndrome fibroblasts. 314 63

An autosomal recessive syndrome is described that associates extreme photosensitivity with a defect of the deoxyribonucleic acid (DNA) excision repair system, mild noncongenital ichthyosis, brittle cystine-deficient hair, impaired intelligence, neurologic disorders, and short stature. A curious very sociable behavior, cataract and retinal dystrophy, recurrent infections, and unusual face are additional features. Fertility may be decreased. This syndrome is related to xeroderma pigmentosum complementation group D but differs from it in the absence of skin tumors, at least in the first two decades of life.
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PMID:PIBI(D)S syndrome--trichothiodystrophy with xeroderma pigmentosum (group D) mutation. 358 77

A normal level of UV-induced DNA-repair synthesis (UDS) was observed in fibroblasts from a patient affected by trichothiodystrophy (TTD) without photosensitivity. This finding indicates that the hypersensitivity to UV light and the reduced UDS due to the presence of xeroderma pigmentosum complementation group D mutation (XP-D), described in photosensitive TTD patients, are not constantly associated with TTD. Complementation analysis in heterokaryons, obtained by fusion of repair-proficient with repair-deficient TTD cells, demonstrates that cells from the patient showing normal photosensitivity are able to restore UDS in UV-hypersensitive TTD cells.
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PMID:Complementation studies in cells from patients affected by trichothiodystrophy with normal or enhanced UV photosensitivity. 360 Jun 93

We studied the response to UV irradiation in cells from four patients, from three apparently unrelated families, affected by trichothiodystrophy (TTD). They showed all the symptoms of this rare autosomal recessive disorder (brittle hair with reduced sulfur content, mental and physical retardation, ichthyosis, peculiar face) together with photosensitivity. We found a decreased rate of duplicative DNA synthesis in stimulated lymphocytes, reduced survival in fibroblasts, and very low levels of unscheduled DNA synthesis (UDS) in Go lymphocytes and fibroblasts after UV irradiation. Complementation studies showed that normal values of UDS are restored in heterokaryons obtained by fusion of TTD cells with normal and xeroderma pigmentosum (XP)-complementation group A-cells. In contrast the defect is not complemented by fusion with XP-complementation group D-fibroblasts.
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PMID:Xeroderma pigmentosum (complementation group D) mutation is present in patients affected by trichothiodystrophy with photosensitivity. 377 Jul 39


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