Biomarker tests of liver, muscle and heart toxicity in vector-treated animals.

Mice were pretreated i.v. with one of two viral vectors as indicated: a) hdAD encoding mCocH (1.7×1012 viral particles), or b) AAV-VIP encoding the human CocH (1013 viral particles). At the same time, control mice received saline injection or no treatment. Three to four months after pretreatment, a saline injection was given and plasma samples were assayed 24 hr later for these biomarkers: ALT (alanine aminotransferase activity, U/L), skeletal muscle troponin-I (SkM-Tn-I, ng/ml), and cardiac troponin-I (C-Tn-I, ng/ml). A week later the same mice were challenged with a large dose of cocaine (120 mg/kg i.p.), and the biomarkers were re-determined after 24 hr. Note the 500-fold rise of plasma ALT in unprotected subjects, ** (p