Table 8.

Mouse (ICR) bone marrow micronucleus tests of the AstraZeneca MEK kinase inhibitor

Agent	Dose (mg/kg)	MNPCE/1000 PCE			% Centromere positive MN from experiment 2
		Experiment 1 (males)	Experiment 1a (females)	Experiment 2b (males)
Vehicle control	0	0.4	0.5	1.15	10
Test agent	500	0.3	0.5	2.55c	82
	1000	0.7	0.5	3.28c	74
	2000	2.5c	2.9c	2.72c	39
CPA (positive control)	50	19.3	21.5	–	–
	65	–		27.5	–

All data is from bone marrows sampled 24 h after oral dosing (no effect at 48 h). PCE: polychromatic erythrocyte; MNPCE: micronucleated PCE; MN: micronuclei; CPA: cyclophosphamide.

^aErythrocytes stained with May–Gruenwald–Giemsa.

^bErythrocytes stained with Acridine Orange.

^cp < 0.05.