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dc.contributor.authorBoyle, John M
dc.date.accessioned2010-12-03T10:36:00Z
dc.date.available2010-12-03T10:36:00Z
dc.date.issued1985-07
dc.identifier.citationPoly (ADP-ribose) metabolism in alkylated mouse L5178Y cells. 1985, 6 (7):1005-9 Carcinogenesisen
dc.identifier.issn0143-3334
dc.identifier.pmid2990753
dc.identifier.doi10.1093/carcin/6.7.1005
dc.identifier.urihttp://hdl.handle.net/10541/117073
dc.description.abstractPoly ADP-ribosylation of two mouse lymphoma cell lines, L5178Y (LS) and the radiation and alkylating agent resistant derivative AII, was investigated by uptake of [3H]NAD by permeabilised cells into acid-precipitable material that was sensitive to phosphodiesterase but insensitive to DNase and RNase. Basal activities in both lymphoma lines were 3-4-fold greater than in mouse L1210 leukaemia cells. However, total endogenous poly (ADP-R) polymerase activity in both L5178Y cell lines, stimulated by a large excess of DNase in the presence of Triton X-100, was less than half the activity in L1210 cells. Doses of N-methyl-N-nitrosourea (MNU) that produced 20-50% survival of colony-forming units increased poly (ADP-R) in both lymphoma lines by only 25% compared with 377% in L1210 cells when synthesis was measured immediately after a 30-min exposure of MNU. During the first 24 h after MNU AII cells produced a peak of activity that was not seen with LS cells. A second peak was seen in both cell lines between 24 and 48 h following MNU. Concentrations of 3-aminobenzamide (3AB) above 2.5 mM inhibited colony-forming ability of lymphoma cells and equally inhibited uptake of [14C]formate into protein, RNA and DNA indicating that 3AB behaves as a general metabolic poison. Concentrations of 3AB in the toxic range of 3-10 mM inhibited poly (ADP-R) synthesis but no degradation of the polymer was observed. Non-toxic concentrations of 3AB potentiated cell killing by MNU to a similar degree in both lymphoma cell lines. In conclusion, we have found little evidence to support the hypothesis that the differential sensitivity of LS and AII is related to poly ADP-ribosylation. Compared with other mouse cells, L5178Y cells appear deficient in poly (ADP-R) polymerase and poly (ADP-R) glycohydrolase activities.
dc.language.isoenen
dc.subjectLeukaemia L1210en
dc.subjectLeukaemia L5178en
dc.subjectExperimental Leukaemiaen
dc.subject.meshAlkylation
dc.subject.meshAnimals
dc.subject.meshCarbon Radioisotopes
dc.subject.meshCell Division
dc.subject.meshFormic Acids
dc.subject.meshKinetics
dc.subject.meshLeukemia L1210
dc.subject.meshLeukemia L5178
dc.subject.meshLeukemia, Experimental
dc.subject.meshMethylnitrosourea
dc.subject.meshMice
dc.subject.meshNAD
dc.subject.meshNAD+ Nucleosidase
dc.subject.meshNitrosourea Compounds
dc.subject.meshNucleoside Diphosphate Sugars
dc.subject.meshPoly Adenosine Diphosphate Ribose
dc.subject.meshPoly(ADP-ribose) Polymerases
dc.titlePoly (ADP-ribose) metabolism in alkylated mouse L5178Y cells.en
dc.typeArticleen
dc.identifier.journalCarcinogenesisen
html.description.abstractPoly ADP-ribosylation of two mouse lymphoma cell lines, L5178Y (LS) and the radiation and alkylating agent resistant derivative AII, was investigated by uptake of [3H]NAD by permeabilised cells into acid-precipitable material that was sensitive to phosphodiesterase but insensitive to DNase and RNase. Basal activities in both lymphoma lines were 3-4-fold greater than in mouse L1210 leukaemia cells. However, total endogenous poly (ADP-R) polymerase activity in both L5178Y cell lines, stimulated by a large excess of DNase in the presence of Triton X-100, was less than half the activity in L1210 cells. Doses of N-methyl-N-nitrosourea (MNU) that produced 20-50% survival of colony-forming units increased poly (ADP-R) in both lymphoma lines by only 25% compared with 377% in L1210 cells when synthesis was measured immediately after a 30-min exposure of MNU. During the first 24 h after MNU AII cells produced a peak of activity that was not seen with LS cells. A second peak was seen in both cell lines between 24 and 48 h following MNU. Concentrations of 3-aminobenzamide (3AB) above 2.5 mM inhibited colony-forming ability of lymphoma cells and equally inhibited uptake of [14C]formate into protein, RNA and DNA indicating that 3AB behaves as a general metabolic poison. Concentrations of 3AB in the toxic range of 3-10 mM inhibited poly (ADP-R) synthesis but no degradation of the polymer was observed. Non-toxic concentrations of 3AB potentiated cell killing by MNU to a similar degree in both lymphoma cell lines. In conclusion, we have found little evidence to support the hypothesis that the differential sensitivity of LS and AII is related to poly ADP-ribosylation. Compared with other mouse cells, L5178Y cells appear deficient in poly (ADP-R) polymerase and poly (ADP-R) glycohydrolase activities.


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