INDUCTION OF ANEUPLOIDY IN CHINESE-HAMSTER OOCYTES FOLLOWING IN-VIVO TREATMENTS WITH TRIMETHOXYBENZOIC COMPOUNDS AND THEIR ANALOGS

Many inhibitors of tubulin polymerization have a trimethoxybenzene rin g in their molecules. Such trimethoxybenzoic compounds and their analo gues may therefore have a potency to induce meiotic nondisjunction of oocytes. In this study, a single dose of reserpine (0.5 mu g/g body we ight), podophyllotoxin (20.0 mu g/g b.w.), trimethoxybenzoic acid (500 .0 mu g/g b.w.) or vinblastine sulfate (3.0 mu g/g b.w.) was injected intraperitoneally to mature female Chinese hamsters at the onset of th e first meiotic spindle formation of oocytes. Within 6 h after spontan eous ovulation, MII oocytes were collected from the oviducts for morph ological examination and cytogenetic analysis. The incidence of morpho logically abnormal oocytes with unusually large first polar body or bo dies increased significantly after the treatment with reserpine (18/20 2; 8.9%), podophyllotoxin (28/172; 16.3%) and vinblastine sulfate (63/ 197; 32.0%), as compared with the control (3/214; 1.4%). Chromosome an alysis of oocytes revealed that podophyllotoxin and vinblastine sulfat e were effective in inducing aneuploidy (62/154; 40.3% and 128/156; 82 .1% vs. 3/198; 1.5% of the control) by inhibiting the formation of spi ndle microtubules at the first meiosis. Aneuploids were found more fre quently in morphologically abnormal oocytes than in normal oocytes. No aneugenic activity of reserpine and trimethoxybenzoic acid was observ ed. These results indicate that trimethoxybenzoic compounds do not nec essarily exhibit aneugenic activity.