Bettina M. Francis
PhD, 1971, University of Michigan, Ann Arbor
Francis is an environmental toxicologist whose work focuses on the irreversible effects of pesticides. One focus of her research is on alterations in gene expression following exposure to environmental agents (broadly defined). By using chemicals that affect gene expression (e.g., retinoic acid) and cause malformations in experimental animals, she attempts both to identify mechanisms by which developmental toxicants cause malformations, and to identify genes acting in normal development.
Francis also has a strong interest in pesticide in toxicology, and especially their irreversible effects. Such studies often intersect the developmental studies. For example, the herbicide nitrofen (2,4-dichlorophenyl 4'-nitrophenyl ether) causes a unique constellation of defects in rodents that is highly suggestive of perturbed gene expression as a primary mechanism.. Nitrofen causes malformations of the kidneys, heart, diaphragm, and Harderian glands if administered to mice on gestational day (GD) 8 development. It does not cause limb malformations, even though our experience shows that most teratogens that cause cell death or decrease cell proliferation will cause limb malformations on GD 8.
Another example is the delayed paralysis that follows exposure to some organophosphorus esters (OPs). In humans, both adults and children can be affected, although children seem to be less sensitive. In chickens, only mature fowl become paralyzed -- chicks do not. However, when chick embryos or very young chicks are exposed to such OPs, long-lastin functional deficits result. In some cases, birds remained abnormal even as adults. Neither the mechanism for the adult paralysis nor for the develmental effects is known.
Additional pesticide studies include comparison of structure-activity relationships among nitrofen analogs and examination of the possibility that pesticides cause endocrine disruption, either by altering estrogen metabolism (DDT) or thyroid function (nitrofen) in developing fetuses and their dams.
Finally, Francis remains interested in the ecological effects of pesticide use, and uses the Metcalf microcosm to investigate these.
Toxic Substances in the Environment: ENVST 331 or CHLTH 361; 3 hours or 3/4 unit.
Developmental Toxicology: ENVST 416 or VB 416, co-taught with S. Schantz (even-numbered years)
Pesticide Toxicology: ENVST 333 or VB 333 (odd-numbered years).
ENVST 331, Toxic Substances in the Environment, is an overview course for people who want (or need) to know some toxicology but do not intend to become toxicologists. Case histories are used to teach basic principles of environmental toxicology, from the causes and effects of global warming to the mechanisms by which a normal cell becomes a cancer cell.
ENVST 333, Pesticide Toxicology, examines the biological effects of major classes of insecticides and herbicides, and of selected individual fungicides.This course should be of interest to graduate students in toxicology, and to graduate or advanced undergraduate students who expect to use pesticides in their occupations (farmers, foresters, veterinarians). It may also be of interest to students in health-related professions because of the continuing clinical of pesticides in occupational andchildhood poisonings.
ENVST 416, Developmental Toxicology, examines the causes and manifestations both of structural malformations (B. Francis) and functional deficits (S. Schantz) in mammals. Topics covered include interactions between external factors and developmental gene expression, the behavioral consequences of chemical exposure, identification and regulation of developmental toxicants. Examples emphasize agents that are present in the human environment. The course requires reading and analysis of the current literature.
Representative and Recent Publications
Francis, B. M., R. A. Lampman and R. L. Metcalf 1985. Model ecosystem studies of the environmental fate of five herbicides used in conservation tillage. Archiv. Environ. Contam. Toxicol. 14, 693-704.
Farage-Elawar, M, J. S. Duffy and B. M. Francis 1991. Developmental toxicity of desbromoleptophos in chicks: enzyme inhibition, malformations and functional deficits. Neurotoxicol. Teratol. 13, 91-97.
Rosen, M., B. M. Francis and N. Chernoff 1994. Subtractive hybridization: a technique for the isolation of differentially expressed genes. Toxicology Methods 4, 135-147.
Rogers, J. M., B. M. Francis, K. K. Sulik, A. J. Alles, K. H. Elstein, R. M. Zucker, E. J. Massaro, M. B. Rosen and N. Chernoff 1994. Cell death and cell cycle perturbation in the developmental toxicity of the demethylating agent, 5-aza-2'-deoxycytidine. Teratology 50, 332- 339.
Chen, S-W, P. J. Dziuk and B. M. Francis 1994. Effect of four environmental toxicants on plasma Ca and estradiol 17 and hepatic P450 in laying hens. Environ. Toxicol. Chem. 13, 789-796.
Rosiak, K. L., M-W. Li, S. J. Degitz, D. Skalla, I. Chu and B. M. Francis 1997. Maternal and developmental toxicity of polychlorinated diphenyl ethers (PCDEs) in Swiss-Webster mice and Sprague-Dawley rats. Toxicology 121, 191-204.
Rosiak, K. L., W. Seo, I. Chu and B. M. Francis 1997. Effects of maternal exposure to chlorinated diphenyl ethers on thyroid hormone concentrations in maternal and juvenile rats. J. Environ. Science Health B 32, 377-393.
Branch, S, B. M. Francis, M. B. Rosen, C. F. Brownie, G. A. Held and N. Chernoff 1998. Differentially expressed genes associated with 5-aza-2'-deoxycytidine-induced hindlimb defects in the Swiss-Webster mouse. J Biochem. Molec. Toxicol. 12, 135-141.
Degitz, S. J., D. Morris, G. L. Foley and B. M. Francis 1998. The role of TGF- in retinoic acid-induced cleft palate in CD-1 mice. Teratology (in press).
Francis, B. M., R. L. Metcalf, P. Lewis and N. Chernoff 1999. Maternal and developmental toxicity of halogenated 4'-nitrophenyl ethers in mice. Teratology (in press).