Abstract
We evaluated whether environmental tobacco smoke exposure in utero and/or postnatally affects the biochemical composition of the brain. Pregnant Sprague-Dawley rats were exposed to filtered air (FA) or to sidestream smoke (SS) for 4 h/d, 7 d/wk from d 3 of pregnancy until delivery, then their female pups were exposed to either FA or SS for 9 wk postnatally. This resulted in four exposure conditions: in utero FA followed by postnatal FA (FA/FA), in utero FA followed by postnatal SS (FA/SS),in utero SS followed by postnatal FA (SS/FA), and in utero SS followed by postnatal SS (SS/SS). After completion of the exposures, the brains were removed and divided at the pontomesencephalic junction into forebrain and hindbrain; each specimen was then analyzed for DNA, protein, and cholesterol concentration. Data were analyzed by 2-way analysis of variance.In utero SS had no effect on these three biochemical measurements. However, postnatal SS reduced hindbrain DNA concentration (an indicator of cellular density) by 4.4% (p = 0.001). In addition, the hindbrain protein/DNA ratio (an index of cell size) was increased in these animals by 8.4% (p = 0.001). Hindbrain weight was not affected by SS exposure, but body weight was reduced by 6.4% (p = 0.016). These data suggest that postnatal exposure to SS affects the hindbrain (a region which undergoes significant postnatal growth) by reducing the total number of cells and by increasing cell size. Hindbrain cellular hypertrophy may help offset the decrease in cell number, thereby leaving hindbrain weight unchanged. Despite preserved hindbrain weight, these effects of postnatal exposure to SS may result in neurologic dysfunction.
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Abbreviations
- ETS:
-
environmental tobacco smoke
- FA:
-
filtered air
- MS:
-
mainstream smoke
- SS:
-
sidestream smoke
REFERENCES
Behnke M, Eyler FD 1993 The consequences of prenatal substance use for the developing fetus, newborn, and young child. Int J Addict 28: 1341–1391.
Butler NR, Goldstein H 1973 Smoking in pregnancy and subsequent child development. BMJ 4: 573–575.
Fergusson DM, Horwood J, Lynskey MT 1993 Maternal smoking before and after pregnancy: effects on behavioral outcomes in middle childhood. Pediatrics 92: 815–822.
Himmelberger DU, Brown BW, Cohen EN 1978 Cigarette smoking during pregnancy and the occurrence of spontaneous abortion and congenital abnormality. Am J Epidemiol 108: 470–479.
Holsclaw DS, Topham AL 1978 The effects of smoking on fetal, neonatal and childhood development. Pediatr Ann 7: 201–221.
Johnston C 1981 Cigarette smoking and outcome of human pregnancies: a status report on the consequences. Clin Toxicol 18: 189–209.
Kristjansson EA, Fried PA, Watkinson B 1989 Maternal smoking during pregnancy affects children's vigilance performance. Drug Alcohol Depend 24: 11–19.
Makin J, Fried PA, Watkinson B 1991 A comparison of active and passive smoking during pregnancy: long-term effects. Neurotoxicol Teratol 13: 5–12.
Olds DL, Henderson CR, Tatelbaum R 1994 Intellectual impairment in children of women who smoke cigarettes during pregnancy. Pediatrics 93: 221–227.
Weitzman M, Gortmaker S, Sobol A 1992 Maternal smoking and behavior problems in children. Pediatrics 90: 342–349.
Chen LH, Petitti DB 1995 Case-control study of passive smoking and the risk of small-for-gestational-age at term. Am J Epidemiol 142: 158–165.
US Department of Health and Human Services 1989 The health consequences of involuntary smoking. A Report of the Surgeon General. DHHS Pub. No. (PHS) 87-8398. US Department of Health and Human Services, Public Health Service, Office of the Assistant Secretary for Health, Office of Smoking and Health, Washington, DC
US Environmental Protection Agency 1992 Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders. EPA/600/6-90/006F. Office of Health and Environmental Assessment, Office of Research and Development, Washington, DC
Overpeck MD, Moss AJ 1991 Children's Exposure to Environmental Cigarette Smoke Before and After Birth: Health of Our Nation's Children. DHHS Pub. No. (PHS) 91-1250. US Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Center for Health Statistics, Hyattsville, MD
Charlton A 1994 Children and passive smoking: a review. J Fam Pract 38: 267–277.
Klonoff-Cohen HS, Edelstein SL, Lefkowitz ES, Srinivasan IP, Kaegi D, Chang JC, Wiley KJ 1995 The effect of passive smoking and tobacco exposure through breast milk on sudden infant death syndrome. JAMA 273: 795–798.
Schoendorf KC, Kiely JL 1992 Relationship of sudden infant death syndrome to maternal smoking during and after pregnancy. Pediatrics 90: 905–908.
Leichter J 1989 Growth of fetuses of rats exposed to ethanol and cigarette smoke during gestation. Growth Dev Aging 53: 129–134.
Rajini P, Last JA, Pinkerton KE, Hendrickx AG, Witschi H 1994 Decreased fetal weights in rats exposed to sidestream cigarette smoke. Fundam Appl Toxicol 22: 400–404.
Witschi H, Lundgaard SM, Rajini P, Hendrickx AG, Last JA 1994 Effects of exposure to nicotine and to sidestream smoke on pregnancy outcome in rats. Toxicol Lett 71: 279–286.
Fung YK 1988 Postnatal behavioural effects of maternal nicotine exposure in rats. J Pharm Pharmacol 40: 870–872.
Mactutus CF 1989 Developmental neurotoxicity of nicotine, carbon monoxide and other tobacco smoke constituents. In: Hutchings ED (ed) Prenatal Abuse of Licit and Illicit Drugs. New York Academy of Sciences, New York, 105–122.
Levin ED, Briggs SJ, Christopher NC, Rose JE 1993 Prenatal nicotine exposure and cognitive performance in rats. Neurotoxicol Teratol 15: 251–260.
Slotkin TA, Cho H, Whitmore WL 1987 Effects of prenatal nicotine exposure on neuronal development: selective actions on central and peripheral catecholaminergic pathways. Brain Res Bull 18: 601–611.
Slotkin TA, Orband-Miller L, Queen KL 1987 Development of [3H]nicotine binding sites in brain regions of rats exposed to nicotine prenatally via maternal injections or infusions. J Pharmacol Exp Ther 242: 232–237.
Van De Kamp JL, Collins AC 1994 Prenatal nicotine alters nicotinic receptor development in the mouse brain. Pharmacol Biochem Behav 47: 889–900.
Fish I, Winick M 1969 Cellular growth in various regions of the developing rat brain. Pediatr Res 3: 407–412.
Winick M, Noble A 1965 Quantitative changes in DNA, RNA, and protein during prenatal and postnatal growth in the rat. Dev Biol 12: 451–466.
Zamenhof S, Ahmad G, Guthrie D 1979 Correlations between neonatal body weight and adolescent brain development in rats. Biol Neonate 35: 273–278.
Zamenhof S, Guthrie D 1977 Differential responses to prenatal malnutrition among neonatal rats. Biol Neonate 32: 205–210.
Navarro HA, Seidler FJ, Schwartz RD, Baker FE, Dobbins SS, Slotkin TA 1989 Prenatal exposure to nicotine impairs nervous system development at a dose which does not affect viability or growth. Brain Res Bull 23: 187–192.
Slotkin TA, Greer N, Faust J, Cho H, Seidler FJ 1986 Effects of maternal nicotine injections on brain development in the rat: ornithine decarboxylase activity, nucleic acids and proteins in discrete brain regions. Brain Res Bull 17: 41–50.
Slotkin TA, Orband-Miller L, Queen KL, Whitmore WL, Seidler FJ 1987 Effects of prenatal nicotine exposure on biochemical development of rat brain regions: maternal drug infusions via osmotic minipumps. J Pharmacol Exp Ther 240: 602–611.
Teague SV, Pinkerton KE, Goldsmith M, Gebremichael A, Chang S, Jenkins RA, Moneyhun JH 1994 A side-stream cigarette smoke generation and exposure system for environmental tobacco smoke studies. Inhalation Toxicol 6: 79–93.
Labarca C, Paigen K 1980 A simple, rapid, and sensitive DNA assay procedure. Anal Biochem 102: 344–353.
Bradford MM 1976 A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254.
Searcy RL, Bergquist LM 1960 A new color reaction for the quantitation of serum cholesterol. Clin Chim Acta 5: 192–199.
Dodge PR, Prensky AL, Feigin RD 1975 Nutrition and the Developing Nervous System. CV Mosby, St. Louis, 24–65.
Engsner G, Vahlquist B 1975 Brain growth in children with protein-energy malnutrition, in Brazier MAB (ed) Growth and Development of the Brain: Nutritional, Genetic, and Environmental Factors. Raven Press, New York, 315–333.
Reinis S, Goldman JM 1980 The Development of the Brain: Biological and Functional Perspectives. Charles C Thomas, Springfield, IL 317–341.
Lazzaroni F, Bonassi S, Manniello E, Morcaldi L, Repetto E, Ruocco A, Calvi A, Cotellessa G 1990 Effect of passive smoking during pregnancy on selected perinatal parameters. Int J Epidemiol 19: 960–966.
Koren G 1995 Fetal toxicology of environmental tobacco smoke. Curr Opin Pediatr 7: 128–131.
Luck W, Nau H, Hansen R, Steldinger R 1985 Extent of nicotine and cotinine transfer to human fetus, placenta and amniotic fluid of smoking mothers. Dev Pharmacol Ther 8: 384–385.
Dobbing J 1981 The later development of the brain and its vulnerability, in Davis JA, Dobbing J (eds) Scientific Foundations of Paediatrics, 2nd Ed. William Heinemann Medical Books Ltd., London, 744–759.
Acknowledgements
The authors thank Drs. J. Joad and A. Clifford for helpful discussions regarding these studies, and Michael Goldsmith for technical assistance with the SS exposures.
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Supported, in part, by the University of California Tobacco-Related Disease Research Program and the NIEHS Environmental Health Sciences Center at the University of California, Davis (Grant ES05707).
This work was presented at the 64th Annual Meeting of the Society for Pediatric Research, San Diego, CA 1995.
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Gospe, S., Zhou, S. & Pinkerton, K. Effects of Environmental Tobacco Smoke Exposure in Utero and/or Postnatally on Brain Development. Pediatr Res 39, 494–498 (1996). https://doi.org/10.1203/00006450-199603000-00018
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DOI: https://doi.org/10.1203/00006450-199603000-00018
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