A comparative study on ethanol and acetaldehyde as inducers of chromosome malsegregation in Aspergillus nidulans.
The activity of ethyl alcohol and acetaldehyde on mitotic chromosome segregation and conidial germination in Aspergillus nidulans was studied. Ethanol effectively induced malsegregation in a narrow range of concentrations (4.5-5.5%, v/v) and was inactive at doses which arrested conidial germination (above 6%). The same bell-shaped dose-response curve was shown by the spindle poison chloral hydrate, which was active in the range 6-10 mM. Acetaldehyde displayed a diphasic dose-response curve. Genetic analysis of induced segregants suggests that the disturbance of chromosome segregation is the primary genetic effect at low doses (0.025-0.037%), while at higher doses (above 0.1%), when growth was arrested, chromosome damage was primarily induced. The same pattern of segregants was produced by hydroquinone, a substance which indirectly affects chromosome segregation in A. nidulans. These differences in the genotoxic profiles of ethanol and acetaldehyde suggest that the effect exerted by ethanol on A. nidulans mitosis is not dependent on its conversion into acetaldehyde. In the absence of an effect of ethanol on in vitro polymerization of tubulin (actively inhibited by acetaldehyde at doses above 0.075%), a direct effect of ethanol on cell membranes is hypothesized. Comparison of the inhibition of growth and the effectiveness in aneuploidy induction displayed by ethanol, methanol, n-propanol and n-butanol demonstrates, in fact, a fair correlation with logP, a descriptor of lipophilicity related to the partitioning of compounds in biological membranes.
Crebelli
R
R
Istituto Superiore di Sanitá, Rome, Italy.
Conti
G
G
Conti
L
L
Carere
A
A
D000079:Acetaldehyde / Q000494:pharmacology*; D000438:Alcohols / Q000494:pharmacology; D000782:Aneuploidy; D001233:Aspergillus nidulans / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects*; D012995:Solubility; D008941:Spindle Apparatus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism
D000438:Alcohols; D014404:Tubulin; D000431:Ethanol; D000079:Acetaldehyde