These changes were accompanied by reduced mRNA and protein expression of the folate-dependent nucleotide-synthesising enzymes thymidylate synthase (TS) and dihydrofolate reductase (DHFR) and suppressed 3H-thymidine uptake mediated by downregulation of thymidine kinase 1 in the cancer cell lines exposed to ADI-PEG20 [12]. The gene discussed is DHFR; the disease is cancer.