Clinical pharmacology of pravastatin, a selective inhibitor of HMG-CoA reductase.

Pravastatin, lovastatin and simvastatin are HMG-CoA reductase inhibitors with very similar structures. However, minor substitutions in the decalin ring have resulted in major differences in physiocochemical, pharmacological, and pharmacokinetic properties. Both in vitro and in vivo studies have demonstrated that lovastatin and simvastatin are non-selective lipophilic inhibitors, while pravastatin is a selective hydrophilic inhibitor.

Activation of H-ras oncogenes in preneoplastic mouse mammary tissues.

The mammary hyperplastic outgrowth (HOG) line C4, resulted from serial transplantation of a hyperplastic alveolar nodule which arose in a dimethylbenz(a)anthracene (DMBA) treated mouse. The immortalized C4 outgrowth line, on transplantation into syngeneic mice, develops as preneoplastic, hyperplastic outgrowths and subsequently into malignant carcinomas after a long latent period (greater than 6 months). Treatment of mice carrying C4 HOG transplants with DMBA resulted in a reduced latent period for tumor development (less than 3 months) and an increased tumor incidence.