General Issues of Variability and Polymorphism

Variability in patterns of drug metabolism has been recognized for some time, even before the discovery of P450s. For instance, the phenomenon of pharmacogenetic variation had been identified by the 1950s and the early work of Remmer showed the influence of barbiturates upon drug metabolism. Further, a number of congenital defects in steroid metabolism were known and some could be attributed to alterations in specific hydroxylations. Much of the subsequent work on inducibility has been done in experimental animal models and later, cell culture. 

Benzo[a]pyrene and other polycyclic hydrocarbons 2-Amino-1 -methyl-6-phenylimidazo-[4,5-i)]pyridine (PhIP) 

2-Amino-6-methy l-dipyrido[ 1,2-a 3,2 -i/ -imidazole (Glu P-1) 2-Aminodipyrido- [l,2-a 3,2 -if imidazole (Glu P-2) 2-Amino-3-methylimidazo-[4,5-/] quinoline (IQ) 

2- Amino-3,5 -dimethy l-imidazo[4,5 -/ ] quinoline (MelQ) 2-Amino-3,8-dimethyl-imidazo[4,5 /]quinoline (MelQx) 

4-(Methylnitrosamino)-l-(3-pyridyl)-l-butano (NNAL) Nomitrosonicotine (NNN) 4-(Methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) 

---