EVALUATION OF THE V79 CELL METABOLIC COOPERATION ASSAY AS A SCREEN INVITRO FOR DEVELOPMENTAL TOXICANTS

Inhibition of intercellular communication is proposed to be one of sev eral possible mechanisms of teratogenesis. 38 coded compounds were tes ted for their effect on intercellular communication in the V79 cell me tabolic co-operation assay. Test chemicals were selected from a list o f 47 agents recommended for the evaluation of assays in vitro for deve lopmental toxicants. In addition to testing the effects of chemicals o n intercellular communication, a separate cytotoxicity assay determine d the concentration of each chemical that inhibited clonal expansion o f V79 cells. Seven of the 29 designated teratogens were positive for i nhibition of intercellular communication in the V79 assay. Additionall y, four teratogens and one non-teratogen inhibited intercellular commu nication at only a single concentration or at cytotoxic concentrations and were scored as equivocal. Therefore, the sensitivity of the V79 a ssay for teratogens was 24% (seven of 29 teratogens tested positive), or 38% if the four equivocal chemicals are considered positive. None o f the nine non-teratogens unequivocally inhibited intercellular commun ication, resulting in a specificity of 100%, which decreased to 89% wh en the single equivocal score was considered positive. The overall acc uracy for correctly identifying teratogens and non-teratogens was 42% when equivocal chemicals were considered negative, and 50% if they wer e considered positive in the V79 assay. The results demonstrate that d espite relatively low accuracy regarding a diverse group of developmen tal toxicants, chemicals that did inhibit intercellular communication under the present conditions had a high probability of being a teratog en. The low accuracy reported here contrasts with earlier reports on t he assay and possible reasons for this are discussed.