In vitro studies of biological effects of cigarette smoke condensate. II. Induction of sister-chromatid exchanges in human lymphocytes by weakly acidic, semivolatile constituents.
Cigarette smoke condensate is known to enhance the frequency of sister-chromatid exchanges (SCE) in human lymphocytes in vitro and some of the activity has been found in the most volatile part of the particulate phase, the semivolatile fraction. In this study we have investigated the chemical composition and the SCE-inducing activity of the weakly acidic, semivolatile fraction of a cigarette smoke condensate. A number of individual weakly acidic compounds were also tested for their SCE-inducing effects. The weakly acidic fraction was separated by preparative gel chromatography into 11 subfractions (F1-F11). The chemical composition was determined by gas chromatography and gas chromatography-mass spectrometry. Measurements of the effects on SCE in human lymphocytes were used to evaluate the genotoxic effects. All fractions except F11 induced SCE in a dose-dependent way. The most active fraction was F4 which contained mainly alkyl-2-hydroxy-2-cyclopenten-1-ones. The individual compounds to be tested for induction of SCE were selected on the basis of their abundance in the weakly acidic subfractions and on the basis of their occurrence in the environment. Of 23 tested compounds, most of which were alkylphenols, 7 induced SCE, i.e., catechol, 2-(1-propenyl)phenol, cyclotene, maltol, isoeugenol, 2-methoxyphenol (guaiacol) and vanillin. Many of these are important flavor components that occur not only in tobacco and tobacco smoke but also in food, candies, beverages and perfumes.
D000143:Acids / Q000302:isolation & purification / Q000494:pharmacology; D001547:Benzaldehydes / Q000494:pharmacology; D005421:Flavoring Agents / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology; D010947:Plants, Toxic; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D012906:Smoke / Q000032:analysis*; D013329:Structure-Activity Relationship; D014026:Nicotiana / Q000032:analysis*
D000143:Acids; D001547:Benzaldehydes; D005421:Flavoring Agents; D010636:Phenols; D012906:Smoke; C100058:vanillin