Source:http://linkedlifedata.com/resource/pubmed/id/12189183
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
|
| pubmed:dateCreated |
2002-8-21
|
| pubmed:abstractText |
Mother-to-child transmission of the human immunodeficiency virus is substantially reduced by prenatal and postnatal treatment with anti-retroviral nucleoside analogues; however, the long-term consequences of these drug interventions are not known. The nucleoside analogue zidovudine (3'-azido-2',3'-dideoxythymidine; AZT) is carcinogenic in mice when administered transplacentally or neonatally, and this may be due to a genotoxic mechanism. Since single-drug treatment with AZT is being superseded by multidrug combinations, we have investigated the induction of mutations and micronuclei in mice treated neonatally with AZT, lamivudine (3'-thia-2',3'-dideoxycytidine; 3TC), or a combination of the two drugs. B6C3F(1)/Tk+/- mice were treated daily from days 1-8 of age with 200 mg AZT/kg/day, 200 mg 3TC/kg/day, or a mixture of 200 mg AZT + 200 mg 3TC/kg/day (AZT/3TC). One and 2 days after the last dose, bone marrow was collected to assess the induction of micronuclei in polychromatic erythrocytes; 3 weeks following treatment, the induction of mutants was determined in the hypoxanthine-guanine phosphoribosyltransferase (Hprt) and thymidine kinase (Tk) genes of spleen lymphocytes. AZT and AZT/3TC, but not 3TC, caused a significant increase in micronuclei, with the response being greatest one day after the last dose. None of the drugs induced mutations in the Hprt gene, while AZT and AZT/3TC, but not 3TC, caused a significant increase in the Tk mutant frequency. The increase in Tk mutants by AZT and AZT/3TC was associated with loss of the wild-type (Tk+) allele (loss of heterozygosity). These data suggest that AZT, but not 3TC, is genotoxic in neonatal mice, and that 3TC does not alter significantly the responses observed with AZT alone.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-HIV Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Bromodeoxyuridine,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxanthine...,
http://linkedlifedata.com/resource/pubmed/chemical/Lamivudine,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Zidovudine
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0143-3334
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
23
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1427-32
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:12189183-Animals,
pubmed-meshheading:12189183-Anti-HIV Agents,
pubmed-meshheading:12189183-Bone Marrow,
pubmed-meshheading:12189183-Bromodeoxyuridine,
pubmed-meshheading:12189183-Drug Interactions,
pubmed-meshheading:12189183-Drug Resistance, Neoplasm,
pubmed-meshheading:12189183-Erythrocytes,
pubmed-meshheading:12189183-Female,
pubmed-meshheading:12189183-Gene Frequency,
pubmed-meshheading:12189183-Hypoxanthine Phosphoribosyltransferase,
pubmed-meshheading:12189183-Lamivudine,
pubmed-meshheading:12189183-Loss of Heterozygosity,
pubmed-meshheading:12189183-Lymphocytes,
pubmed-meshheading:12189183-Male,
pubmed-meshheading:12189183-Mice,
pubmed-meshheading:12189183-Mice, Inbred C57BL,
pubmed-meshheading:12189183-Mice, Transgenic,
pubmed-meshheading:12189183-Micronuclei, Chromosome-Defective,
pubmed-meshheading:12189183-Mutation,
pubmed-meshheading:12189183-Thymidine Kinase,
pubmed-meshheading:12189183-Zidovudine
|
| pubmed:year |
2002
|
| pubmed:articleTitle |
Frequency of Tk and Hprt lymphocyte mutants and bone marrow micronuclei in B6C3F(1)/Tk+/- mice treated neonatally with zidovudine and lamivudine.
|
| pubmed:affiliation |
Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA.
|
| pubmed:publicationType |
Journal Article
|