p53 accumulates in micronuclei after treatment with a DNA breaking chemical, methylnitrosourea, and with the spindle poison, vinblastine.
Micronuclei (MN) induced by N-methyl-N-nitrosourea (MNU) or vinblastine in cultured mammalian cells were analyzed for the accumulation of p53 by immunocytochemical staining with a p53 monoclonal antibody. Our data showed that MN induced by both agents were p53-negative at early post-treatment times, but became positive at late times. Assuming that most MNU-induced micronuclei reflect DNA damage, and most vinblastine-induced micronuclei reflect damage to the mitotic apparatus, we conclude that p53 accumulation in micronuclei is not triggered by DNA damage per se but instead probably stems from DNA degradation occurring during ageing of micronuclei.
Granetto
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IST, National Institute for Research on Cancer, Genoa, Italy.
Ottaggio
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Abbondandolo
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Bonatti
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D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004171:Diploidy; D005347:Fibroblasts; D006801:Humans; D008770:Methylnitrosourea / Q000494:pharmacology*; D048629:Micronuclei, Chromosome-Defective / Q000737:chemistry*; D009153:Mutagens / Q000494:pharmacology*; D008941:Spindle Apparatus / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D014747:Vinblastine / Q000494:pharmacology*
D000477:Alkylating Agents; D009153:Mutagens; D016159:Tumor Suppressor Protein p53; D014747:Vinblastine; D008770:Methylnitrosourea