INDUCTION OF TERATA IN HAMSTERS BY SOLANIDANE ALKALOIDS DERIVED FROM SOLANUM-TUBEROSUM

The potential induction of terata by solanidanes has been of public he alth concern since a report in 1972 hypothesized that certain birth de fects in humans could be attributed to ingestion of blighted potatoes. The potential teratogenicity of solanidane alkaloids from potatoes an d tomatoes in domestic livestock had been considered even earlier. In the present report, oral administration of the steroidal alkaloid glyc osides alpha-solanine and alpha-chaconine and their aglycone solanidin e is shown to induce craniofacial malformations (exencephaly, encephal ocele, and anophthalmia) in Syrian hamsters. All three alkaloids, that were either isolated or obtained by hydrolysis from Solanum tuberosum (var. Kennebec) sprouts, possessed the 22(R),25(S)-configuration in t he indolizidine moiety with no other isomers present. Toxicity constra ints precluded administration of dosages high enough to induce statist ically significant levels of terata in litters dosed with alpha-chacon ine and permitted the attainment of only marginal statistical signific ance for alpha-solanine. However, malformation induction at p < 0.005 was observed in litters upon dosing both the nontoxic aglycone solanid ine and the derivative solanidine N-oxide at higher levels. The relati vely high teratogenicity of nontoxic solanidine, compared to the glyco sides, demonstrates that terata induction by solanidanes is not due to maternal toxicity nor is the oligosaccharide portion of steroidal alk aloid glycosides required to facilitate passage of the teratogen to th e fetus. The teratogenicity of solanidine N-oxide, a putative metaboli te, suggests that N-oxidation is not an effective mammalian detoxifica tion pathway. Relative teratogenic potencies (RTP) were assigned to so lanidanes by conversion of literature data to equimolar doses compared to the powerful Veratrum teratogen jervine and the nonteratogenic spi rosolane tomatidine. RTP values are as follows: jervine(100), 22(S), 2 5(R)-solanidanes (50), alpha-chaconine (43), alpha-solanine (32), 22(R ),25(S)-solanidine (32), solanidine N-oxide (32), 5 alpha,6-dihydrosol anidine (9), and tomatidine (0).