In vitro studies of aldehyde effects related to human respiratory carcinogenesis.
Aldehydes are ubiquitous compounds which are generated from many both endogenous and exogenous sources. Primarily because certain aldehydes are respiratory toxicants and carcinogens in laboratory animals, and also because they are present in both tobacco smoke and automotive emissions, cultured human bronchial cells have been used to study the ability of aldehydes, i.e., acrolein and formaldehyde, to cause pathobiological effects associated with carcinogenesis. Comparative studies indicate that each aldehyde distinctly affects several molecular and cellular variables including colony-forming efficiency, clonal growth rate, membrane integrity, formation of cross-linked envelopes, levels of cytosolic free calcium, low-molecular-weight thiol status, DNA structure, i.e., formation of DNA single-strand breaks and DNA-protein cross-links, and various DNA repair mechanisms. In relation to the toxicity exerted by these agents, acrolein induces differentiation more readily than formaldehyde whereas formaldehyde causes much higher levels of genetic damage than acrolein. However, for all biological endpoints measured, acrolein on a molar basis is always more potent than formaldehyde. Taken together, a variety of effects that relate to cell death, accelerated epithelial terminal differentiation and genotoxicity are associated with aldehyde exposure, which in human airways may have a role in the pathogenesis of various diseases. In the development of cancer, the possible contribution of aldehydes from both intra- and extra-cellular sources may partly depend on the ability of target cells to detoxify and counteract those aldehyde-related effects believed to critically relate to multi-stage carcinogenesis.
Grafström
R C
RC
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
D000171:Acrolein / Q000633:toxicity; D000447:Aldehydes / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D005557:Formaldehyde / Q000633:toxicity; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000447:Aldehydes; D013438:Sulfhydryl Compounds; D005557:Formaldehyde; D000171:Acrolein; D002118:Calcium