GENETIC TOXICITY STUDIES OF 1,2,3,4-TETRAHYDRO-9-ACRIDINAMINE (TACRINE)

The mutagenicity and clastogenicity of 1,2,3,4-tetrahydro-9-acridinami ne (tacrine) were studied in vitro using the Salmonella mutagenicity t est and the induction of chromosome aberrations in Chinese hamster ova ry (CHO) cells, and in the mouse bone marrow micronucleus test in vivo . This chemical is currently being used to treat dementia arising from Alzheimer's Disease, Tacrine was mutagenic in Salmonella but did not produce chromosome damage in CHO cells or in mouse bone marrow cells. A clear mutagenic response was seen in strain TA97 with rat and hamste r liver S9; inconsistent results were obtained without S9, No mutageni city was seen in strains TA98 and TA100 without S9, and inconsistent r esults were seen with S9. There was no induction of chromosome aberrat ions in cultured CHO cells with or without S9, Oral administration to mice of tacrine daily for three days did not result in the induction o f micronuclei in their bone marrow cells. The mutagenic response in Sa lmonella, and the structure of the molecule, suggests that tacrine may be carcinogenic when tested in rodents. This information must be cons idered when preparing benefit-risk determinations for medical uses of this substance. (C) 1997 Elsevier Science B.V.