Table 1.
Characteristics of morphologic assays and percent of agents that tested positive*
| Assay | Model/inducer | Criteria for a positive result† | Positive/total agents (% positive) |
|---|---|---|---|
| ACF | F344 rats/AOM | Statistically significant (P < .05) decrease in ACF | 152/244 (62) |
| A427 | Human lung carcinoma cells/NA | ≥20% inhibition of anchorage-independent colony formation at one or more concentrations | 253/336 (75) |
| HFE | Neonatal human foreskin epidermal cells/PS | ≥30% growth inhibition; or ≥20% involucrin induction; or ≥20% PCNA† expression inhibition – at two consecutive, nontoxic concentrations | 57/65 (88) |
| JB6 | Mouse epidermal cells/TPA | Statistically significant (P < .05) decrease in anchorage-independent colony formation | 60/110 (54) |
| MMOC | BALBc mammary glands/DMBA | ≥60% decrease of hyperplastic nodules | 184/350 (53) |
| RTE | F344 tracheal epithelial cells/B[a]P | ≥20% inhibition of transformed foci at two or more nontoxic concentrations | 283/388 (73) |
* The six morphologic assays comprise five in vitro assays: rat tracheal epithelial cell (RTE), human lung tumor A427 cell (A427), mouse mammary organ culture (MMOC), mouse JB6 epidermal cell (JB6), and human foreskin epithelial cell (HFE); and one in vivo assay: aberrant crypt foci (ACF) in rats (1). The best result for each agent in each assay was incorporated into the statistical model. To fit a good statistical model, a reasonable percent of agents should test negative as well as positive in a given morphologic assay. If the percent testing positive is too high, less discrimination is achieved among tested agents. A427 = human lung tumor A427 cell; ACF = aberrant crypt foci; AOM = azoxymethane; B[a]P = benzo[a]pyrene; DMBA = 7,12-dimethylbenz[a]anthracene; HFE = human foreskin epithelial cell; JB6 = mouse JB6 epidermal cell; MMOC = mouse mammary organ culture; RTE = rat tracheal epithelial cell; NA = not applicable; PS = propane sultone; PCNA = proliferating cell nuclear antigen; TPA = tetradecanoylphorbol acetate.
† Each endpoint is evaluated in comparison with the vehicle or solvent control. Of the 552 agents, 484 were positive in at least one assay.