NTP report on the toxicology and carcinogenicity study of mixtures of 3'-Azido-3'-Deoxythymidine (AZT), lamivudine (3TC), and nevirapine (NVP) (CAS NOs 30516-87-1, 134678-17-4, 129618-40-2) in genetically modified c3B6.129F1-Trp53tm1Brd N12 haploinsufficient mice (In utero and postnatal gavage study)
METHODS: We exposed groups of haploinsufficient C3B6.129F1-Trp53tm1Brd N12 mice by depositing solutions containing AZT, 3TC, NVP, or combinations of the drugs in a methylcellulose solvent directly into the animals' stomachs through a tube twice daily for 28 days following birth; in addition, th...
| Corporate Author: | |
|---|---|
| Other Authors: | |
| Format: | eBook |
| Language: | English |
| Published: |
Research Triangle Park, NC
National Toxicology Program
October 2013, 2013
|
| Series: | NTP GMM
|
| Online Access: | |
| Collection: | National Center for Biotechnology Information - Collection details see MPG.ReNa |
| Summary: | METHODS: We exposed groups of haploinsufficient C3B6.129F1-Trp53tm1Brd N12 mice by depositing solutions containing AZT, 3TC, NVP, or combinations of the drugs in a methylcellulose solvent directly into the animals' stomachs through a tube twice daily for 28 days following birth; in addition, their mothers were exposed to the drug for seven days during pregnancy. Other sets of mothers and pups received only the methylcellulose solvent and served as the control groups. Following the dosing period, the animals were observed until 45 weeks of age. Tissues from 34 organs were examined for every animal. RESULTS: Exposure to AZT caused increases in the rates of liver cancer (hepatocellular adenoma) in the male pups after 45 weeks; groups of males receiving AZT and 3TC or AZT, 3TC, and NVP also had increased rates of hepatocellular adenomas and carcinomas. In addition, there were occurrences of a few malignant lymphomas in male pups receiving AZT or AZT, 3TC, and NVP and in female pups receiving NVP, AZT plus 3TC, or the three drugs combined. CONCLUSIONS: We conclude that AZT either alone or in combination with 3TC or with 3TC and NVP caused liver cancers in male pups exposed before and following birth. Malignant lymphomas in male and female pups may have been related to exposure to AZT alone or in combination with 3TC before and following birth BACKGROUND: 3' Azido-3'-deoxythymidine (AZT) is the most widely used chemotherapeutic agent for the treatment of people with acquired immune deficiency syndrome (AIDS) or positive for the human immunodeficiency virus (HIV). AZT treatment is also given to prevent transmission of HIV from pregnant mothers to children before or during birth, and current treatments involve combinations of drugs. Among the most commonly used are lamivudine (3TC) and nevirapine (NVP). We tested the effects of these three drugs, both individually and in combination, on the offspring of female mice (genetically modified to be sensitive to cancer induction) where the mothers were given the drugs during pregnancy. |
|---|---|
| Physical Description: | 1 PDF file (236 pages) illustrations |