Drug used to prevent HIV transmission from mother to child damages DNA

Studies demonstrate that AZT causes genetic damage that may increase future cancer risk

HIV transmission from mother to child can occur in utero, during labor or from breastfeeding. If left untreated, approximately 25 percent of newborns exposed to the virus from their infected mothers will become infected themselves and potentially develop AIDS. Fortunately, antiretroviral drug combinations, which typically include AZT (zidovudine), a nucleoside reverse transcriptase inhibitor (NRTI), have reduced the rate of transmission from mother to child to less than 2 percent in infants who are not breast fed.

NRTIs work by inhibiting the viral reverse transcriptase and by incorporating into the viral DNA and terminating nascent strands, thus preventing the virus from duplicating. However, previous research has shown that NRTIs also incorporate into the DNA of host cells, causing damage that could have long-term health consequences for those exposed to the drugs.

Two new animal studies have examined the cancer-causing effects of transplacental exposure to AZT in mice and rats and found increased rates of tumors and tumors with gene changes that frequently occur in human cancer. In addition, two human studies are the first to observe the induction of mutations and large scale chromosomal damage in red blood cells of newborns exposed to NRTIs in utero.

These, and other, studies were published in April 2007 in a special issue of Environmental and Molecular Mutagenesis that examines the latest research on DNA damage and potential health risks related to the use of NRTIs. Besides the effects of NRTIs on nuclear DNA and cancer risk, the issue also contains recent findings on the toxicity of these drugs toward mitochondrial DNA. Environmental and Molecular Mutagenesis, the official journal of the Environmental Mutagen Society, is published by John Wiley & Sons, Inc. and is available online via Wiley InterScience at (http://www.interscience.wiley.com/journal/emm).

Researchers led by Dale M. Walker of Experimental Pathology Laboratories in Herndon, VA, administered AZT in varying doses to female mice and rats during the last 7 days of gestation and examined the tissue of their offspring two years later. They found clear evidence of an AZT-induced increase in the incidence of hemangiosarcoma (cancer originating in cells that line the blood vessels) in male mice and mononuclear cell leukemia in female rats.

There was also some evidence of increased liver cancer and reproductive tumors. "Although the implications of these findings for the long-term health of human children exposed tranplacentally to AZT are uncertain, the possibility of increased cancer risk for a subset of these children in mid and late adulthood appears highly plausible," the authors state. The carcinogenic effects of AZT were further demonstrated by a study on mice led by Hue-Hua Hong of the National Institute of Environmental Health Sciences in Research Triangle Park, NC. This study found mutations in the K-ras and p53 cancer genes that are often mutated in human lung tumors. The development of lung cancer in these mice suggests that the incorporation of AZT or its metabolites into DNA, oxidative stress, and genomic instability may be the contributing factors to the pattern of mutations observed in the study, according to the authors. They conclude, "The cumulative mutagenesis data suggest that infants exposed transplacentally to AZT may be at increased risk for cancer as they age."