Niacin deficiency increases the sensitivity of rats to the short and long term effects of ethylnitrosourea treatment
Most chemotherapy agents function by causing damage to the DNA of rapidly dividing cells, such as those in the bone marrow, leading to anemia and leukopenia during chemotherapy and the development of secondary leukemias in the years following recovery from the original disease. We created an animal...
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| Veröffentlicht in: | Molecular and cellular biochemistry 1999-03, Vol.193 (1/2), p.83-87 |
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| creator | Boyonoski, A.C Gallacher, L.M ApSimon, M.M Jacobs, R.M Shah, G.M Poirier, G.G Kirkland, J.B |
| description | Most chemotherapy agents function by causing damage to the DNA of rapidly dividing cells, such as those in the bone marrow, leading to anemia and leukopenia during chemotherapy and the development of secondary leukemias in the years following recovery from the original disease. We created an animal model of nitrosourea-based chemotherapy using ethylnitrosourea (ENU) to investigate the effect of niacin deficiency on the side effects of chemotherapy. Weanling Long-Evans rats were fed diets containing various levels of niacin for a period of 4 weeks. ENU treatment started after 1 week of feeding and consisted of 12 doses delivered by gavage, every other day. Cancer incidence was also monitored in the following months. ENU treatment caused many of the acute symptoms seen in human chemotherapy patients, including anemia and neutropenia. Niacin deficiency (ND) had several interesting effects, alone and in combination with ENU. Niacin deficiency alone caused a modest anemia, while in combination with ENU it induced a severe anemia. Niacin deficiency alone caused a 4-fold increase in circulating neutrophil numbers, and this population was drastically reduced by ENU-treatment. In the long term, macin deficiency caused an increased incidence of cancer, especially chronic granulocytic leukemias. |
| doi_str_mv | 10.1023/A:1006964227277 |
| format | Article |
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We created an animal model of nitrosourea-based chemotherapy using ethylnitrosourea (ENU) to investigate the effect of niacin deficiency on the side effects of chemotherapy. Weanling Long-Evans rats were fed diets containing various levels of niacin for a period of 4 weeks. ENU treatment started after 1 week of feeding and consisted of 12 doses delivered by gavage, every other day. Cancer incidence was also monitored in the following months. ENU treatment caused many of the acute symptoms seen in human chemotherapy patients, including anemia and neutropenia. Niacin deficiency (ND) had several interesting effects, alone and in combination with ENU. Niacin deficiency alone caused a modest anemia, while in combination with ENU it induced a severe anemia. Niacin deficiency alone caused a 4-fold increase in circulating neutrophil numbers, and this population was drastically reduced by ENU-treatment. In the long term, macin deficiency caused an increased incidence of cancer, especially chronic granulocytic leukemias.</description><identifier>ISSN: 0300-8177</identifier><identifier>EISSN: 1573-4919</identifier><identifier>DOI: 10.1023/A:1006964227277</identifier><identifier>PMID: 10331642</identifier><language>eng</language><publisher>Netherlands: Springer Nature B.V</publisher><subject>Age Factors ; Anemia - prevention & control ; Animal diseases ; Animal models ; Animals ; Bone marrow ; Chemotherapy ; Drug Interactions ; drug therapy ; Drug Therapy, Combination ; Ethylnitrosourea - therapeutic use ; leukopenia ; Leukopenia - prevention & control ; Male ; Medical research ; Neoplasms, Experimental - drug therapy ; Neoplasms, Experimental - metabolism ; niacin ; Niacin - deficiency ; Niacin - pharmacology ; Rats ; Rats, Long-Evans ; Rodents ; vitamin deficiencies</subject><ispartof>Molecular and cellular biochemistry, 1999-03, Vol.193 (1/2), p.83-87</ispartof><rights>Kluwer Academic Publishers 1999</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c236t-e635f3e4e2e90a0a4ac1f5977aeef48350d122c0a98a2986138d5d25e904acca3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10331642$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Boyonoski, A.C</creatorcontrib><creatorcontrib>Gallacher, L.M</creatorcontrib><creatorcontrib>ApSimon, M.M</creatorcontrib><creatorcontrib>Jacobs, R.M</creatorcontrib><creatorcontrib>Shah, G.M</creatorcontrib><creatorcontrib>Poirier, G.G</creatorcontrib><creatorcontrib>Kirkland, J.B</creatorcontrib><title>Niacin deficiency increases the sensitivity of rats to the short and long term effects of ethylnitrosourea treatment</title><title>Molecular and cellular biochemistry</title><addtitle>Mol Cell Biochem</addtitle><description>Most chemotherapy agents function by causing damage to the DNA of rapidly dividing cells, such as those in the bone marrow, leading to anemia and leukopenia during chemotherapy and the development of secondary leukemias in the years following recovery from the original disease. We created an animal model of nitrosourea-based chemotherapy using ethylnitrosourea (ENU) to investigate the effect of niacin deficiency on the side effects of chemotherapy. Weanling Long-Evans rats were fed diets containing various levels of niacin for a period of 4 weeks. ENU treatment started after 1 week of feeding and consisted of 12 doses delivered by gavage, every other day. Cancer incidence was also monitored in the following months. ENU treatment caused many of the acute symptoms seen in human chemotherapy patients, including anemia and neutropenia. Niacin deficiency (ND) had several interesting effects, alone and in combination with ENU. Niacin deficiency alone caused a modest anemia, while in combination with ENU it induced a severe anemia. Niacin deficiency alone caused a 4-fold increase in circulating neutrophil numbers, and this population was drastically reduced by ENU-treatment. In the long term, macin deficiency caused an increased incidence of cancer, especially chronic granulocytic leukemias.</description><subject>Age Factors</subject><subject>Anemia - prevention & control</subject><subject>Animal diseases</subject><subject>Animal models</subject><subject>Animals</subject><subject>Bone marrow</subject><subject>Chemotherapy</subject><subject>Drug Interactions</subject><subject>drug therapy</subject><subject>Drug Therapy, Combination</subject><subject>Ethylnitrosourea - therapeutic use</subject><subject>leukopenia</subject><subject>Leukopenia - prevention & control</subject><subject>Male</subject><subject>Medical research</subject><subject>Neoplasms, Experimental - drug therapy</subject><subject>Neoplasms, Experimental - metabolism</subject><subject>niacin</subject><subject>Niacin - deficiency</subject><subject>Niacin - pharmacology</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Rodents</subject><subject>vitamin 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We created an animal model of nitrosourea-based chemotherapy using ethylnitrosourea (ENU) to investigate the effect of niacin deficiency on the side effects of chemotherapy. Weanling Long-Evans rats were fed diets containing various levels of niacin for a period of 4 weeks. ENU treatment started after 1 week of feeding and consisted of 12 doses delivered by gavage, every other day. Cancer incidence was also monitored in the following months. ENU treatment caused many of the acute symptoms seen in human chemotherapy patients, including anemia and neutropenia. Niacin deficiency (ND) had several interesting effects, alone and in combination with ENU. Niacin deficiency alone caused a modest anemia, while in combination with ENU it induced a severe anemia. Niacin deficiency alone caused a 4-fold increase in circulating neutrophil numbers, and this population was drastically reduced by ENU-treatment. 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| fulltext | fulltext |
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| ispartof | Molecular and cellular biochemistry, 1999-03, Vol.193 (1/2), p.83-87 |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Age Factors Anemia - prevention & control Animal diseases Animal models Animals Bone marrow Chemotherapy Drug Interactions drug therapy Drug Therapy, Combination Ethylnitrosourea - therapeutic use leukopenia Leukopenia - prevention & control Male Medical research Neoplasms, Experimental - drug therapy Neoplasms, Experimental - metabolism niacin Niacin - deficiency Niacin - pharmacology Rats Rats, Long-Evans Rodents vitamin deficiencies |
| title | Niacin deficiency increases the sensitivity of rats to the short and long term effects of ethylnitrosourea treatment |
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