The ability to detect and quantitate DNA damage at a cellular level is of major importance in evaluating the consequences of human exposure to drugs and other chemicals. Damage to DNA, leading to mutation, is implicated in the development of numerous adverse health effects, including both cancer and birth defects. Commonly abused substances, such as tobacco and marijuana, are known to contain potentially mutagenic chemicals, but it has been difficult to obtain direct evidence of the genotoxic effects of these substances in humans. The current burden of human disease caused by DNA-damaging agents could be better understood, and more effectively reduced, if sensitive tests were available for specific, early identification of genetically hazardous human exposures. The autoradiographic hprt mutant T-lymphocyte assay is a test that has recently been refined and validated and is now available for use in studying individuals who are exposed to genotoxic drugs. The hprt assay has not yet been applied, to any extent, to the study of groups of pregnant women. However, detection of genetic alterations resulting from the abuse of mutagenic substances by pregnant women is of special importance because of the need to protect the fetus from exposure to genotoxins. The proposed research will involve study of gene mutations in both pregnant women and their newborns. The hypotheses to be investigated are (1) Pregnant women who smoke either marijuana cigarettes or tobacco cigarettes will have increased frequencies of specific-locus mutations in their T-lymphocytes, when compared to non-smoking pregnant women and (2) Marijuana smoking and tobacco smoking during pregnancy will result in an increase in the frequencies of mutant lymphocytes in cord blood from newborns of smoking mothers when compared to newborns of non-smokers. These hypotheses will be tested by determining the frequencies of hprt mutant cells in blood samples from a tri-ethnic group of women who attend prenatal clinics operated by The University of Texas Medical Branch. Maternal blood samples from the two groups of smokers and from non-smokers will be obtained early in pregnancy and again at the end of pregnancy. Samples of fetal placental cord blood will be obtained at delivery. Mutation assays will be done with viable, cryopreserved cells, to allow maternal and fetal lymphocytes to be assayed concurrently for detection of the mutagenic effects of abuse of marijuana or tobacco.
| Ammenheuser, M M; Berenson, A B; Babiak, A E et al. (1998) Frequencies of hprt mutant lymphocytes in marijuana-smoking mothers and their newborns. Mutat Res 403:55-64 |
| Ammenheuser, M M; Hastings, D A; Whorton Jr, E B et al. (1997) Frequencies of hprt mutant lymphocytes in smokers, non-smokers, and former smokers. Environ Mol Mutagen 30:131-8 |
