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)

Repair replication was examined in cultured human cells exposed to the hepatocarcinogen aflatoxin B1 using the combined bromodeoxyuridine density label and radioisotopic label method. Semiconservative DNA synthesis was strongly inhibited, and the repair replication mode was stimulated in diploid fibroblasts (W138) and in their SV40 transformants (VA13) only when exposure to aflatoxin B1 was in the presence of an activating system containing rat liver microsomal enzymes. The maximum amount of repair synthesis was about 20% of that obtained after saturating doses of ultraviolet light (UV). The time course of repair synthesis was similar to that seen after UV, and most of the synthesis was in 30- to 50-nucleotide "short patches." A line of SV40-transformed xeroderma pigmentosum cells (Group A) deficient in repair after exposure to UV was similarly deficient in repair replication after aflatoxin treatment. Treatment with aflatoxin resulted in a 25 to 45% inhibition of UV-induced repair replication, suggesting that in addition to producing lesions in DNA, which are substrates for the excision repair system, the toxin also inhibits excision repair. CsC1 gradients of DNA treated in vitro with activated aflatoxin demonstrated binding of the drug to DNA. Alkaline sucrose gradient sedimentation gave no indication that single-strand breaks or alkali labile bonds were introduced into DNA by treatment of cells with activated aflatoxin.
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PMID:Repair of DNA in human cells after treatment with activated aflatoxin B1. 19 62

Under the specific conditions reported for the separate tests delta9-tetrahydrocannabinol (THC) did not elicit a mutagenic response in microbial and eukaryotic in vitro test systems. THC treatment to histidine auxotrophs of Salmonella typhimurium strains TA 98 (susceptible to frame shift mutation) and TA 100 (susceptible to base pair substitution) were investigated. Analysis for possible revertance in the presence and absence of S9 microsomal activation system indicated an absence of induction of gene mutation. Cultured fibroblasts from healthy individuals and DNA repair deficient Xeroderma pigmentosum patients display similar survival activity upon exposure to THC. There was no observable increase in the number of chromosome breaks or chromatid exchanges following exposure to THC or THC plus S9 microsomal fraction. THC, 11-OHdelta9-THC, cannabinol, and cannabidiol did not induce unscheduled DNA repair synthesis in cultured human fibroblasts. Moreover, THC did not suppress UV-induced DNA repair synthesis.
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PMID:Nonmutagenic action of cannabinoids in vitro. 35 30

At doses varying from 8 x 10(-5) to 3 x 10(-3) M sodium selenite (Na2SeO3) induced DNA fragmentation, DNA-repair synthesis, chromosome aberrations and a mitotic inhibition in cultured human fibroblasts. The response of DNA repair-deficient xeroderma pigmentosum (XP) fibroblasts to selenite is comparable to that of control cells. Incubation with mouse liver S-9 microsomal fraction increased the capacity of selenite to induce chromosome aberrations, DNA-repair synthesis and a lethal effect. XP cells behaved as control cells when treated with activated selenite. Sodium selenate (Na2SeO4) at doses ranging from 8 x 10(-5) to 3 x 10(-3) M could not be activated by incubating with a S-9 preparation. Selenate had the capacity to induce a small but significant DNA-repair synthesis.
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PMID:The mutagenicity and cytotoxicity of selenite, "activated" selenite and selenate for normal and DNA repair-deficient human fibroblasts. 63 5

The activation of the mycotoxins aflatoxin B1, G1, B2, G2, aflatoxicol and sterigmatocystin by 9S fraction, microsomal preparation (105,000 times g) and supernatant (105,000 times g) of livers of several species was examined. DNA repair synthesis, chromosome aberrations and clone forming capacity were used as endpoints. Cultured fibroblasts of normal persons and DNA repair deficient Xeroderma pigmentosum patients were employed as test subjects. The activation mixtures significantly increase the chromosome breaking function, lethality and DNA damaging effect (measured as DNA repair synthesis) of aflatoxin B1, G1, aflatoxicol ans sterigmatocystin. The DNA repair-deficient XP cells respond to the activated mycotoxins with a low level of unscheduled 3HTdR incorporation as compared to that of control cells, but show a highly elevated sensitivity to the chromosome-damaging and lethal effect of aflatoxin B1 and sterigmatocystin.
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PMID:The response of Xeroderma pigmentosum cells and controls to the activated mycotoxins, aflatoxins and sterigmatocystin. 117 27