A preliminary assessment of the toxic and mutagenic potential of steroidal alkaloids in transgenic mice

Impregnated CD2 transgenic mice, which contain multiple copies of a λgt10lacZ construct integrated into the genome of each cell, were given a predetermined estimated maximum tolerated dose of several steroidal alkaloids: Solanum glycoalkaloids from potato, α-chaconine and α-solanine; aglycones, solanidine and solasodine, and a Veratrum alkaloid, jervine. Observations were made of dams and foetuses for indications of toxicity and/or terata; some dam livers and foetuses were assayed for mutagenicity using the lacZ gene. Other dams were gavaged with a single dose of 75 mg all-trans-retinol/kg to serve as a reference teratogen. Unexpectedly, this level of retinol was not clearly teratogenic. The results of both positive and non-positive selection systems showed that the mutation frequencies in the livers of the dams dosed with α-chaconine, α-solanine and solanidine were three to four times higher than historically normal in the livers of this transgenic mouse strain.