Cells exhibiting the multidrug resistance (MDR) phenotype demonstrate a dec
reased intracellular drug accumulation due to an active outward transport a
nd decreased intracellular flux. This study demonstrates the inhibition of
MDR in mussel (Mytilus edulis) embryos and larvae based on a simple bioassa
y. The development of embryos was assessed and abnormalities identified at
key stages of development, including gastrulation, trochophore and prodisso
conch stages. The incidence of developmental abnormalities was significantl
y increased in the presence of vinblastine, MMS, chloroquine, mitomycin-C,
cadmium chloride and colchicine, compared to clean seawater. Consistently,
there was a further increase in the number and severity of deformities obse
rved when each toxin was added in the presence of verapamil. Larval growth
was also significantly impaired in the presence of verapamil. Increased acc
umulation of fluorescent MDR dyes, such as rhodamine B, has been measured a
nd shown to be verapamil sensitive. This bioassay encompasses a period of i
ntense cellular activity during which the impairment of a number of critica
l processes results in abnormal growth and development. (C) 2000 Elsevier S
cience Ltd. All rights reserved.