There is evidence that some of the toxicity of these pHAHs may be directly due to CYP1A activity; for example, CYP1A2 knockout mice are resistant to liver damage and uroporphyria when exposed to TCDD (Smith et al.
Protection of the CYP1a2 null mouse against uroporphyria and hepatic injury following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
CYP1a1(-/-) male mice: protection against high-dose TCDD-induced lethality and wasting syndrome, and resistance to intrahepatocyte lipid accumulation and uroporphyria. Toxicol Appl Pharmacol 196:410-421.
Cyp1a2(-/-) mice also appear to be completely protected from hepatic uroporphyria caused by dioxin, hexachlorobenzene, and iron overload, although metabolism of these chemicals does not seem to be involved in the mechanism of their toxicity (Sinclair et al.
Uroporphyria produced in mice by iron and 5-aminolaevulinic acid does not occur in Cyp1a2(-/-) null mutant mice.