P450 and human cancer.

Most of the chemical carcinogens in our environment are activated mainly by a restricted number of cytochrome P450 species, P450 1A1, 1A2, 2E1, and 3A. This metabolic activation of procarcinogens is a crucial part of the initial host response to the environmental exposure, since most chemical carcinogens do not show any carcinogenicity by themselves. Inter-individual variability in the metabolic activity may thus be a key host factor to explain the differences in susceptibility to chemical carcinogenesis among individuals. Recent studies on P450s in cancer etiology have provided some valuable insights into this problem.

2,3,7,8 ‐tetrachloro‐dibenzo‐p‐dioxin

xenobiotics‐responsive element

basic transcription element

aryl hydrocarbon hybroxylase

2 ‐aminoanthracene

2‐aminofluorene

2‐acetyl‐aminofluorene

4‐aminobiphenyl

2‐naph‐thylamine

3‐ amino‐1,4‐dimethyl –5H‐ pyrido[4,3‐b]‐indole

3‐amino‐l‐methyl‐5H‐pyrido [4,3‐b] indole

2 – amino – 6 – methyJdipy rido [1,2 –a: 3′,2′–d] imidazole

2‐aminodipyrido[l,2‐a:3′,2′‐d] imidazole

2‐amino‐3‐methylimidazo[4,5‐f|quinoline

2‐amino‐3,5‐dimethylimidazo[4,5‐if]quinoline

2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline

2‐amino‐3,4,8‐trimethylimidazo[4,5‐f|quinoxaHne

N‐nitrosodimethylamine

nitrosoamines

chloramphenicol acetyltransferase

N‐nitrosodiethylamine