A toxic dose reaches simulated hepatocytes and immediately perturbs a small panel of stress-response genes (UPR, oxidative-stress, DNA-damage-response, xenobiotic-metabolism, synthetic-function genes). Their expression shifts within hours — long before any cell has actually died.
Blood ALT (a conventional liver-injury marker) only rises once enough hepatocytes have accumulated irreversible damage and started leaking enzyme into circulation. That takes an accumulated dose of sustained stress, which is why it lags days behind the molecular signature.
gene panel: responds ~ hours (fast, reversible signal)
blood ALT: responds ~ days (slow, cumulative damage)
lead time = day(ALT crosses abnormal) − day(panel crosses alert)
- Dose — higher dose drives both timelines faster, but the biomarker panel keeps its head start because it only needs a signal, while ALT needs actual accumulated cell rupture.
- Low doses may nudge the gene panel without ever pushing ALT out of the normal range — an adaptive response, not injury.
- This is an illustrative model of a real toxicogenomics concept, not a validated clinical predictor.