The pathogenesis of vacuoles produced in rat and mouse liver cells by a conjugate of adenine arabinoside monophosphate with lactosaminated albumin

A conjugate of adenine arabinoside monophosphate with lactosaminated albumin produced vacuoles in hepatic cells of rats and mice when given at doses 5–10 times higher than that (35 mg/kg) capable of inhibiting hepatitis B virus replication in patients with chronic hepatitis B. The vacuoles were due to the swelling of secondary lysosomes probably caused by incapacity of the lysosomal enzymes to rapidly digest large amounts of conjugate into products able to cross the lysosomal membrane. Although vacuoles progressively disappeared when conjugate administration was discontinued, the present observation suggests caution in giving the conjugate to man at daily doses higher than 35 mg/kg.