Advertisement

Cell Biology and Toxicology

, Volume 1, Issue 1, pp 173–193 | Cite as

An evaluation of the utility of four in vitro short term tests for predicting the cytotoxicity of individual compounds derived from tobacco smoke

  • Margareta Curvall
  • Curt R. Enzell
  • Bertil Pettersson
Article

An evaluation of results obtained earlier and now complemented to provide information on the activity of 305 compounds in four in vitro tests has been undertaken. Biological data based on the effects of these compounds on cell multiplication, oxidative metabolism, ciliary activity and membrane permeability are compared with a view to clarifying intersystem similarities and differences and, on the basis of a mean activity parameter, evaluating structure-activity and functionality-activity relationships.

High mean activity is observed for 59 compounds, of which 18 are phenols, 14 aldehydes, 8 N-heterocyclics, 7 alcohols and 5 hydrocarbons. The medium and low mean activity groups comprise 105 and 131 members, respectively, and both include representatives of all functionalities examined. Delineation of the 305 compounds using 45 descriptors, and computer-assisted matching of these and any combination of them against the mean activity showed the most toxic single descriptor group to be terpenoids followed by indoles and naphthalenes, and the most toxic two-descriptor group to be α, β-unsaturated carbonyls followed by n-alkyl alcohols, aldehydes and acids.

Examination of intersystem similarities and differences, using a high-medium-low scale, shows that all four systems give the same result for 35 percent of the compounds, three systems for 41 to 48 percent of the compounds, and two systems for 53 to 64 percent of the compounds. Of all compounds, 16 percent exhibit a high activity in one system and a low activity in the other three, or vice versa. Nearly, half od these discrepancies are caused by the membrane permeability system showing diverging results, while none of them are related to the brown fat cell system. The last test system is found to best represent the mean activity obtained from the four systems and the one of choice if reducing the number of tests from four to one.

Key Words

Toxicity screening cytotoxic effects in vitro short term tests inhibition of cell growth inhibition of oxidative metabolism membrane damage ciliotoxicity compounds derived from tobacco smoke test system comparison 

Abbreviations

CG

cell growth

OM

oxidative metabolism

MD

membrane damage

CA

ciliary activity

A

biological activity

AT

mean activity of four individual test system values (ACG, AOM, AMD, and ACA)

ATN

mean activity for N number of compounds

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. BAUERLEIN, E. AND TRASCH, H. (1979). Interactions between alkyl chains with and without functional groups and beef heart mitochondria. Evidence for the inhibition of proton translocation linked to electron transport. XXI. International Conference on the Biochemistry of lipids, p. 32. Cologne, Germany.Google Scholar
  2. BORENFREUND, E. AND BOORRERO, O. (1984). In vitro cytotoxicity assays: Potential alternatives to the Draize ocular irritancy test. Cell Biology and Toxicology I 1:33–39.Google Scholar
  3. DEICHMANN, W.B. AND KEPLINGER, M.L. (1981). Phenols and phenolic compounds. In Patty's Industrial Hygiene and Toxicology, Vol. 2A (G.D. Clayton and F.E. Clayton, eds), pp. 2567–2627. New York: J. Wiley & Sons.Google Scholar
  4. EKWALL, B. (1980). Screening of toxic compounds in tissue culture. Toxicology 17:127–142.Google Scholar
  5. MUNCH, N., DE RECONDO, A.M. AND FRAYSSINET, C. (1973). Effects of acrolein on DNA synthesis in vitro. Febs. Lett. 30:286–292.Google Scholar
  6. PATEL, J.M., HARPER, C. AND DREW R.T. (1978). Biotransformation of xylene to a toxic aldehyde. Drug Metab. Dispos. 6:368–372.Google Scholar
  7. PETTERSSON, B., CURVALL, M. AND ENZELL, C.R. (1980). Effects of tobacco smoke compounds on the noradrenaline induced oxidative metabolism in isolated brown fat cells. Toxicology 18:1–15.Google Scholar
  8. PETTERSSON, B., CURVALL, M. AND ENZELL, C.R. (1982). Effects of tobacco smoke compounds on the ciliary activity of the embryo chicken trachea in vitro. Toxicology 23:41–55.Google Scholar
  9. PILOTTI, A., ANCKER, K., ARRHENIUS, E. AND ENZELL, C.R. (1975). Effects of tobacco smoke constituents on cell multiplication in vitro. Toxicology 5:49–62.Google Scholar
  10. ROWE, V.K. AND MCCOLLISTER, S.B. (1981). Alcohols, In Patty's Industrial Hygiene and Toxicology, Vol. 2C (G.D. Clayton and F.E. Clayton, eds.), pp. 4527–4708. New York: J. Wiley & Sons.Google Scholar
  11. SANDMYER, E.E (1981). Aromatic hydrocarbons. In Patty's Industrial Hygiene and Toxicology, Vol. 2B (G.D. Clayton and F.E. Clayton, eds.), pp. 3253–3431. New York: J. Wiley & Sons.Google Scholar
  12. SCHAUENSTEIN, E., ESTERBAUER, H. AND ZOLLNER, U. (1977). Aldehydes in Biological Systems, Their Natural Occurrence and Biological Activities, p. 205. London: Pion Limited.Google Scholar
  13. THELESTAM, M., CURVALL, M. AND ENZELL, C.R. (1980). Effect of tobacco smoke compounds on the plasma membrane of cultured human lung fibroblasts. Toxicology 15:203–217.Google Scholar
  14. VAN DEN BERGH, S.G. (1966). The oxidation of fatty acids by intact rat liver mitochondria. In Regulation of Metabolic Processes in Mitrochondria (J.M. Tager, S. Papa, E. Quagliariello and E.C. Slater, eds.), B.B.A. Library, 7, pp. 125–133. Amsterdam: Elsevier Publishing Company.Google Scholar
  15. WILLIAMS, R.T. (1959). Detoxication Mechanisms. 2nd edn., p. 296. New York: J. Wiley & Sons.Google Scholar

Copyright information

© Princeton Scientific Publishers, Inc 1984

Authors and Affiliations

  • Margareta Curvall
    • 1
  • Curt R. Enzell
    • 1
  • Bertil Pettersson
    • 2
  1. 1.Research DepartmentSwedish Tobacco CompanyStockholmSweden
  2. 2.Division of Cellular Toxicology, Environmental Toxicology Unit, Wallenberg LaboratoryUniversity of StockholmStockholmSweden

Personalised recommendations