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1.
DNA Repair (Amst) ; 83: 102640, 2019 11.
Article in English | MEDLINE | ID: mdl-31331821

ABSTRACT

Protein calorie malnutrition (PCM) occurs when insufficient nutrients are consumed to satisfy the biological needs of an organism. The literature supports the relationship between malnutrition and DNA damage, and among the injuries to genetic material, DNA double-strand breaks (DSBs) are the most dangerous. This study aimed to determine whether the ability of splenic and peripheral blood T and B lymphocytes from nursing rats to recognize DSB-induced DNA damage is affected by PCM. Wistar strain rats were used, and experimental malnutrition was induced by creating food competition during lactation by increasing the number of offspring per wet nurse. Due to its high specificity, the phosphorylated H2AX variant histone assay associated with pATM (Ser1981) combined with flow cytometry was herein used to demonstrate the impact of malnutrition on the DNA damage response. Flow cytometry data indicated that splenic T and B lymphocytes from rats with severe PCM have the capacity to detect genetic material damage, as shown by an increased number of pATM + cells and altered signaling pathway continuity. Collectively, these data suggest that severe malnutrition compromises the continuity of the DNA damage response.


Subject(s)
Ataxia Telangiectasia Mutated Proteins/metabolism , B-Lymphocytes/metabolism , Histones/metabolism , Malnutrition/immunology , Malnutrition/metabolism , Phosphoproteins/metabolism , T-Lymphocytes/metabolism , Animals , Body Weight , Phosphorylation , Rats , Rats, Wistar , Spleen/immunology
2.
Bioorg Chem ; 69: 71-76, 2016 12.
Article in English | MEDLINE | ID: mdl-27693943

ABSTRACT

Michael additions between carbohydrate derived nitroalkenes and several aliphatic and aromatic amines proceeded in a stereoselective way, leading to peracetylated 2-amino-1,2-dideoxy-1-nitro-heptitols. In addition, the antiproliferative activity of some of the new adducts has been studied. The results allowed to identify lead compounds which show GI50 values in the range 1.7-19µM.


Subject(s)
Antineoplastic Agents/pharmacology , Sugar Acids/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Structure-Activity Relationship , Sugar Acids/chemical synthesis , Sugar Acids/chemistry
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