The induction of tyrosine aminotransferase (TAT) in the HTC hepatoma cell line is observed after a single administration of an active steroid. A few minutes of contact between the cells and dexamethasone or corticosterone is sufficient to induce TAT synthesis to its maximal level. When radiolabeled hormones are used, no radioactivity is found in the cell one hour after removal of the hormone from the culture medium, whereas TAT activity remains optimal. Thus, the hormone behaves like a start signal for the optimal synthesis of the enzyme and its continuous presence in the medium is not necessary during the whole induction cycle.

More and more numerous each year, and only rarely beneficial, these are responsible for unexplained therapeutic failures or complications. They may occur at different levels. In the bottle of infusion fluid, the risk is that of neutralisation of varying amounts of the antibiotic. At the physiological stages of pharmacokinetics, there may be reduction of absorption and modification of urinary excretion. The most striking iatrogenic consequences result either from competition for binding to plasma albumins or from induction (or inhibition) of hepatic enzymes responsible for biotransformation (toxic overdose). Within bacteria, these interactions explain synergisms and antagonisms. They should lead to awareness of the multiple dangers of polypharmacy.

Enzyme induction by isoniazid was studied by urinary D-glucaric acid estimation in slow and fast acetylators. Isoniazid administration increases significantively the D-glucaric acid elimination in the two classes of patients. In fast acetylators, the glucaricaciduria increases regularly up to 1.8 fold the physiological level in 30 days. In slow acetylators, after a progressive elevation during 20 days, the glucaricaciduria reaches quickly a 3 fold increase after 30 days. When a classic inducer such as phenobarbital is administrated in association with isoniazid, induction is stimulated in the two groups of patients. The estimation of plasmatic free isoniazid seems to indicate that the acetylation rate of isoniazid is not on the dependance of the induction process when the drug is administrated alone. In contrast, this rate increases when the association isoniazid-phenobarbital is administrated to slow acetylators. Possible consequences on the hepatic toxicity of isoniazid are discussed.

Deviation of cortisol metabolism in favour of its 6 beta-hydroxylated derivative was demonstrated in two patients with adrenal failure receiving substitution corticosteroid therapy and rifampicin. The existence of a frank increase in the metabolic clearance antipyrin was in favour of an hepatic enzyme induction. After rifampicin treatment was stopped, the 24 hour urinary excretion of 6 beta-OH-F returned to normal, demonstrating the responsability of the drug. This enzyme induction results in a need to increase the dose of hydrocortisone substitution therapy in patients with Addison's disease treated with rifampicin.

Two platinum derivatives, cis-PtCl2(NH3)2 and PtCl6(NH4)2 have been studied for their effects on the Rat on cytochrome P450 in hepatic parenchyma on zoxazolamine-hydroxylase, a typical inducible system and on the two isoenzymes of dimethyl-nitrosamine demethylase, typical repressible systems. The inhibitory effect of PtCl6(NH4)2 on zoxazolamine-hydroxylase activity, previously shown by the authors, has been confirmed. The cis-PtCl2(NH3)2 also significantly inhibits zoxazolamine-hydroxylase activity. On the other hand, both of the platinum derivatives decrease cytochrome P450 level and enhance the dimethyl-nitrosamine metabolism. These various effects and their relationship are discussed.

Increase of hepatic tyrosine-alpha-ketoglutarate transaminase is observed in Rats (Wistar strain) after intraperitoneal administration of tricyclic compounds (phenothiazin and related structure derivatives). This is an induction process: actinomycine D inhibits this effect. This action is not mediated by glucocorticoids: induction persists in adrenalectomized Rats. The mechanism of action is different too: additive effects are found after simultaneous injection of glucocorticoid and tricyclic drug.

We have showed induction of tyrosine-alpha-ketoglutarate transaminase in hepatic cytosol of Rats (Wistar strain) five hours after intraperitoneal administration of tricyclic compounds (phenothiazine, iminodibenzyl, thioxanthene, thiophenylpyridylamin, dibenzocycloheptadiene, dibenzoxepin derivatives). Chemical structure of these molecules is very important: sulfur atom (phenothiazine, thioxanthene), some substituants like chlorine (chlorpromazine, chlorprothixene) and 2'-dimethylaminopropyl chain (promethazine) increase this inductive effect.

Phenobarbital administration to the Cat an animal hypersensitive to the actions of many toxic substances or to physiological compounds such as hormones, does not produce cytochrome P 450 induction. Consequently, hepatic storage of retinol remains unchanged. The specific and original characteristics of the Cat in this field are underlined by these results.

A 5 P. 100 level of protein from casein in a diet does not allow vitamin A to modify significantly induction of cytochrome P 450 on the Rat receiving or not receiving DDT. When the protein increases to a 15 p. 100 level, the induction is better providing vitamin A is to be given. If protein and vitamin A are necessary for cytochrom P 450 induction, an increase of protein level remains inefficient without vitamin A.