Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043346 (xeroderma pigmentosum)
 2,924 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We propose that SF derived from normal-appearing biopsies of ACR gene carriers exist in an initiated state as the result of a dominant mutation. Based on our studies with the ACR cell system, we further suggest that, although an initiated state is essential to cancer development, not all initiated cells necessarily develop into cancerous cells. The genetic makeup of an initiated cell has been established through linkage between abnormal phenotypic markers and pedigree profiles and through cell hybridization, including initial analysis of gene products. We believe that it is consistent with an autosomal dominant trait. In contrast, cells from patients who are homozygous for chromosomal breakage syndromes, including those with xeroderma pigmentosum, represent an experiment of nature which presumably underlies factors associated with cancer promotion in humans. We have demonstrated that ACR cells can be differentially transformed by oncogenic viruses, a carcinogen (MNNG), and gamma-ray irradiation, and that they can proliferate in vitro after exposure to a tumor promoter (TPA. This simple experimental model provides a novel system for the study of tumor promotion in vitro. We further suggest that, through the use of TPA, various stages associated with cancer development in humans, i.e., initiation through promotion and progression, can be identified in vitro. Attempts to apply these results in vivo are currently in progress. The apparent susceptibility of ACR cells to further transformation by oncogenic viruses and chemical and physical agents indicates that genetic information residing within these cells, probably in the form of a relatively limited and specific number of DNA sequences associated with the ACR mutation, renders them more sensitive to these three distinct classes of carcinogens. We submit that, through our tests on SF, and ACR gene carriers within recognized ACR clusters can be diagnosed at present with sufficient certainty to warrant immediate action. In addition, it seems that the time has arrived for a major undertaking to screen for persons who are likely to be at increased risk of cancer, perhaps through walk-in clinics. An underlying assumption in these studies is that predisposition to cancer, in general, is associated with an autosomal dominant trait in obligatory heterozygote gene carriers.
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PMID:Hereditary adenomatosis of the colon and rectum: relevance to cancer promotion and cancer control in humans. 704 11

The effects of hydroxyurea on plaque formation by UV-irradiated and MNNG-treated adenovirus 5 were investigated. Hydroxyurea blocked the recovery of UV-irradiated viruses in all cases studied, but the effect was less when fibroblasts from a patient with xeroderma pigmentosum were used. This fact supports the notion that hydroxyurea blocks excision repair of UV-produced damage. The recovery of MNNG-treated viruses was not blocked by hydroxyurea when viruses were used to infect normal human fibroblasts, but was blocked if the cell strain used as viral host were deficient in repair of O6-methylguanine. To account for these data, we propose that hydroxyurea blocks repair in which DNA polymerases play a role, but does not block repair in which DNA polymerases are not required.
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PMID:Differential effects of hydroxyurea on the survival of UV- and MNNG-treated adenovirus 5. 711 Jan 76

The UV-endonuclease approach to detect DNA damage has been combined with the alkaline elution technique with a resultant marked increase in sensitivity compared to the conventional method using alkaline sedimentation. DNA from UV-irradiated cells was digested on an inert filter with an extract from Micrococcus luteus and then analyzed by alkaline elution. Endonuclease-sensitive sites (endo-sites) were measured after doses of 0.08-0.7 Jm-2 of UV-radiation. An estimate of endo-site production with UV radiation, 0.27 endo-sites/10(8) daltons of DNA/0.1 Jm-2, was similar to that usually seen at higher doses by others. With repair incubation, approx. 50% of the endo-sites were removed in 4 h by normal human fibroblasts after 0.2 or 0.4 Jm-2; no appreciable repair was seen in xeroderma pigmentosum fibroblasts from complementation group A after 24 h of repair incubation. No photoreaction of UV damage due to 0.4 Jm-2 was detected in normal human fibroblasts. The endonuclease preparation also recognized DNA damage produced by ionizing radiation or an alkylating agent. Approx. 0.4 endo-sites/10(8) daltons of DNA were detected after a dose of 1 krad and 1 endo-site/10(8) daltons was observed after exposure of human cells to 2.5 microM MNNG for 1.3 h. The lesions detected after MNNG treatment by the endonuclease preparation decreased with post-treatment incubation--T1/2 8 h. The kinetics of removal of the endo-sites induced by MNNG were similar in normal cells and human cells of the mer- phenotype which has been shown to be more sensitive by cell killing to alkylating-agent damage. This should prove to be a useful approach to study DNA damage and repair since the entire assay can be done in several hours and a very low level of damage (1 endo-site/2 x 10(9) daltons of DNA) can be detected.
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PMID:Measurement of M. luteus endonuclease-sensitive lesions by alkaline elution. 711 Jan 77

A rearranged tpr-met oncogene was identified in a MNNG-transformed human Xeroderma pigmentosum (XP) cell line (ASKMN). A 2016 bp cDNA was cloned and sequenced, disclosing an ORF with a coding capacity for a 523 aa protein. The sequence of this tpr-met cDNA was very similar to that previously reported in another human MNNG-transformed cell line (MNNG-HOS).
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PMID:Cloning and sequencing of a tpr-met oncogene cDNA isolated from MNNG-transformed human XP fibroblasts. 854 7