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 lambda gt10lacZ construct integrated into the genome of each cell, were given a predetermined estimated maximum tolerated dose of several steroidal alkaloids: Solanum glycoalkaloids from potato, alpha-chaconine and alpha-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 alpha-chaconine, alpha-solanine and solanidine were three to four times higher than historically normal in the livers of this transgenic mouse strain.
Crawford
L
L
US Department of Agriculture, Agricultural Research Service, Western Regional Research Center, Albany, CA 94710.
Myhr
B
B
D000470:Alkaloids / Q000633:toxicity*; D000818:Animals; D004144:Diosgenin; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000235:genetics; D007763:Lac Operon / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D011247:Pregnancy; D012991:Solanaceous Alkaloids / Q000633:toxicity; D012992:Solanine / Q000031:analogs & derivatives / Q000633:toxicity; D011198:Solanum tuberosum / Q000737:chemistry / Q000378:metabolism; D013723:Teratogens / Q000633:toxicity*; D014212:Tretinoin / Q000633:toxicity; D014704:Veratrum Alkaloids / Q000633:toxicity
D000470:Alkaloids; D012991:Solanaceous Alkaloids; D013723:Teratogens; D014704:Veratrum Alkaloids; C010206:jervine; D012992:Solanine; C011860:alpha-chaconine; D014212:Tretinoin; D004144:Diosgenin; C012037:solasodine; C013255:solanidine