Increase In Tyrosine Aminotransferase Activity Research Articles

Effect of Mifepristone on Glucocorticoid Receptor Gene Expression in the Liver of Rats with Streptozotocin-Induced Diabetes

The effects of mifepristone on activity of the adrenocortical system, expression of glucocorticoid receptor gene, and tyrosine aminotransferase activity in the liver were studied in rats with streptozotocin-induced diabetes. Administration of glucocorticoid receptor blocker mifepristone to rats without diabetes was followed by a 1.9-fold increase in serum corticosterone concentration and a 1.2-fold increase in tyrosine aminotransferase activity in the liver in comparison with the baseline values. In rats with streptozotocin-induced diabetes, mifepristone produced a less pronounced increase in the corticosterone concentration (by 1.5 times) and more drastic increase in enzyme activity (by 1.7 times). Mifepristone administration did not change the content of glucocorticoid receptor mRNA in the liver of rats without diabetes, but increase this parameter by 1.4 times in rats with streptozotocin-induced diabetes. The enhanced expression of glucocorticoid receptor gene in the liver of rats with streptozotocin-induced diabetes correlated with increased activity of tyrosine aminotransferase after mifepristone treatment.

Dual Effect of Exogenous Progesterone on the Activity of Tyrosine Aminotransferase in the Liver of Female Rats

An as yet undescribed biphasic response of liver tyrosine aminotransferase (TAT) activity to a single administration of a microcrystallic watery suspension of 25 mg of progesterone (Agolutin Depot, SPOFA Praha) is described in adult female rats subjected to immobilization stress for 150 min. Exaggeration of the stress induced increase of TAT activity 3 and 8 h after hormone administration and its suppression 20 h after it was observed. The stress induced serum corticosterone increase is not correlated with the described changes, however, in non-stressed animals an increased TAT activity at 3 and 8 h after progesterone injection tightly follows the increased plasma corticosterone values. No statistically significant changes were found with respect to liver tryptophan pyrrolase activity.

Vitamin B12deficiency results in the abnormal regulation of serine dehydratase and tyrosine aminotransferase activities correlated with impairment of the adenylyl cyclase system in rat liver

The aim of the present study was to elucidate the mechanism of the vitamin B(12) deficiency-induced changes of the serine dehydratase (SDH) and tyrosine aminotransferase (TAT) activities in the rat liver. When rats were maintained on a vitamin B(12)-deficient diet, the activities of these two enzymes in the liver were significantly reduced compared with those in the B12-sufficient control rats (SDH 2.8 (sd 0.56) v. 17.5 (sd 6.22) nmol/mg protein per min (n 5); P < 0.05) (TAT 25.2 (sd 5.22) v. 41.3 (sd 8.11) nmol/mg protein per min (n 5); P < 0.05). In the B(12)-deficient rats, the level of SDH induction in response to the administration of glucagon and dexamethasone was significantly lower than in the B(12)-sufficient controls. Dexamethasone induced a significant increase in TAT activity in the primary culture of the hepatocytes prepared from the deficient rats, as well as in the cells from the control rats. However, a further increase in TAT activity was not observed in the hepatocytes from the deficient rats, in contrast to the cells from the controls, when glucagon was added simultaneously with dexamethasone. The glucagon-stimulated production of cAMP was significantly reduced in the hepatocytes from the deficient rats relative to the cells from the control rats. Furthermore, the glucagon-stimulated adenylyl cyclase activity in the liver was significantly lower in the deficient rats than in the controls. These results suggest that vitamin B(12) deficiency results in decreases in SDH and TAT activities correlated with the impairment of the glucagon signal transduction through the activation of the adenylyl cyclase system in the liver.

Role of glucocorticoids and resident liver macrophages in induction of tyrosine aminotransferase

Administration of cortisol to an animal induces tyrosine aminotransferase (TAT) in the liver. A similar effect was observed after stimulation of resident liver macrophages (Kupffer cells) by dextran sulfate. Actinomycin D completely blocks enzyme induction both by cortisol and dextran sulfate, whereas their combined effect gives an additive result. In primary culture of hepatocytes, dextran sulfate inhibits TAT activity, but conditioned macrophage medium reliably increases enzyme activity in hepatocytes. However, incubation of isolated macrophages in the presence of dextran sulfate and such medium transfer into hepatocyte culture results in even more pronounced increase in TAT activity. In a combined culture of hepatocytes and non-parenchymal liver cells, reproducing intercellular interactions in vitro, cortisol and non-parenchymal cells exhibit an additive effect on TAT activity. These results show that liver macrophages release a factor of unknown nature launching the mechanism of TAT induction independently of cortisol, a classic TAT inducer.

Hepatic tyrosine aminotransferase activity is affected by chronic heat stress and dietary tyrosine in broiler chickens

1. Two experiments were conducted to investigate the impact of high temperature and dietary tyrosine (Tyr) content on performance and activity of hepatic tyrosine aminotransferase (EC 2.6.1.5.), an enzyme that catalyses the first step in the metabolic degradation of Tyr in broiler chickens. 2. Two-week-old birds were allocated to one of three temperature treatments: 24 ° C (control), 36 ° C (heat stress, HS) and 24 ° C pair-fed (24PF) for 2 weeks and fed on diets containing 100% (Experiment 1) and 50, 100 and 200% (Experiment 2) of the NRC requirement for Tyr. 3. In Experiment 1, exposure of chickens to 36 ° C for 2 weeks caused significant increase in hepatic tyrosine aminotransferase activity but no significant change in activity of hepatic phenylalanine 4-hydroxylase (EC 1.14.16.1) (an enzyme that catalyses conversion of phenylalanine to Tyr) compared with the 24PF birds. No significant changes attributable to heat stress were detected in hepatic glutamic-oxaloacetic transaminase (EC 2.6.1.1) activity. 4. In Experiment 2, heat stress caused reductions in weight gain and feed intake in chickens on all diets, compared with their control counterparts. Hepatic tyrosine aminotransferase activity was increased by heat stress compared with their 24PF counterparts in chickens fed on the 100 and 200% Tyr diets, while in chickens fed the 50% Tyr diet, it was reduced by heat stress. 5. From these results, it is suggested that hepatic tyrosine aminotransferase activity is affected by heat stress and dietary Tyr content and the increased tyrosine aminotransferase activity with, in part, relatively low phenylalanine hydroxylase activity in hepatic tissues may be involved in the Tyr metabolism characteristic of heat-stressed chickens.

Ursodeoxycholic Acid Enhances Glucocorticoid-Induced Tyrosine Aminotransferase-Gene Expression in Cultured Rat Hepatocytes

Ursodeoxycholic acid (UDCA) is an effective treatment for immune-mediated liver diseases, suggesting that UDCA is functionally similar to glucocorticoids (GCs). We investigated the effects of UDCA on the enzyme activity and the mRNA levels of tyrosine aminotransferase (TAT), a hepatocyte-specific marker of GC action, in primary cultured rat hepatocytes. Addition of UDCA resulted in a significant increase in TAT activity in the presence of dexamethasone (DEX), compared with DEX alone, and this increase was completely suppressed by sphingosine, a protein kinase C (PKC) inhibitor, or actinomycin D, a transcriptional inhibitor. UDCA could not induce TAT activity in the absence of DEX. UDCA increased the TAT mRNA levels in the presence of DEX. In conclusion, UDCA enhances the GC-induced TAT-gene expression in hepatocytes, and UDCA-activated PKC may play a role in this upregulation.

Development of dexamethasone-inducible tyrosine aminotransferase activity in WB-F344 rat liver epithelial stemlike cells cultured in the presence of sodium butyrate.

Sodium butyrate acts as a differentiation-promoting agent for a wide variety of cell types, including some tumor cell lines. In this study, we examined the effects of sodium butyrate (SB) on the functional differentiation of cultured WB-F344 rat liver epithelial stemlike cells. Treatment of WB-F344 cells with 3.75 mM SB resulted in an inhibition of cellular proliferation, alterations to normal cellular morphology (increased cell size and decreased nuclear/cytoplasmic ratio), and significant increases in cellular protein synthesis. The SB-mediated changes in cell morphology, proliferative status, and protein catabolism were accompanied by development of dexamethasone-inducible tyrosine aminotransferase (TAT) enzyme activity. Culture of WB-F344 cells in growth medium containing SB and dexamethasone (DEX; 1 x 10(-6) M) resulted in greater than sevenfold increase in the basal TAT activity compared with control cultures. An additional sixfold increase in TAT activity was observed when cells cultured in medium containing SB and DEX were exposed to 1 x 10(-7) M DEX during the last 24 hours of culture. The DEX-inducible TAT activity developed by SB-treated WB-F344 cells responded to the modulating effects of insulin and L-tyrosine in a manner that closely resembled that reported for cultured hepatocytes and hepatoma cell lines. These studies show that treatment of WB-F344 rat liver epithelial stemlike cells with the differentiation-promoting agent SB in vitro leads to expression of the differentiation-specific hepatocyte enzyme TAT.

Regulation of tyrosine aminotransferase activity by glucagon and cAMP analogues in chick embryos in ovo

Glucagon, dibutyryl cAMP (Bt2cAMP) and 8-(4-chlorophenylthio) cAMP (CptcAMP), singly or when combined, stimulated tyrosine aminotransferase (TAT) activity in 17-day-old chick embryos in ovo. Maximal induction was produced within 4 hr of injection of the inducers. The effects of glucagon and the cAMP analogues were not additive. Glucagon administration was accompanied by a rapid increase in hepatic cAMP concentration which remained elevated for at least 4 hr. The stimulated increase in TAT activity elicited by the hormone or cyclic nucleotide was prevented by injection of cycloheximide or cordycepin. These results are discussed vis-à-vis the possible regulation of TAT in ovo by physiological concentrations of glucagon and the likely role of cAMP as a second messenger in this process during chick embryogenesis.

Short- and long-term effects of insulin on tyrosine aminotransferase gene expression

In the present study the relationship between changes in tyrosine aminotransferase (TAT) enzyme activity, cytoplasmic mRNA levels, and gene transcription in response to both short- and long-term exposure to insulin was investigated. Insulin acutely inhibited transcription of the TAT gene by 50% in serum-deprived rat H4 hepatoma cells. Following this initial 50% decrease in transcription, there was a 2.5-fold induction in TAT activity that could not be accounted for by a concomitant increase in TAT mRNA levels. Insulin had no effect on the half-life of TAT mRNA. Insulin exposure for short periods of time also inhibited the glucocorticoid- and cAMP-induced transcription of the TAT gene. Like insulin, protein synthesis inhibitors acutely inhibited basal and glucocorti-coid-induced TAT transcription. TAT activity gradually returned toward basal levels after 8 h of insulin treatment. A second insulin-induced increase in TAT activity (3.5-fold above basal levels) was observed by 24 h of insulin treatment. This second phase of insulin-induced TAT activity was associated with elevated levels of TAT transcription and TAT mRNA levels, and, therefore, unlike the earlier stimulation, could be accounted for by changes in gene expression. Thus, the insulin-mediated regulation of the TAT gene in H4 cells is complex. Different transcriptional and post-transcriptional mechanisms are likely to be involved in the biphasic responses to insulin.

Studies on the anti-allergic mechanism of glucocorticoids in mice.

Glucocorticoids inhibit IgE antibody-mediated passive cutaneous anaphylaxis (PCA) and chemical mediator-induced cutaneous reactions elicited in the mouse ear. In the present study, we investigated the effect of actinomycin D, a protein synthesis inhibitor, on dexamethasone-caused inhibition of PCA and histamine-induced cutaneous reaction in the mouse ear. Tyrosine aminotransferase (TAT) activity in the liver, which was estimated as an index for protein synthesis, significantly increased by the administration of hydrocortisone, prednisolone and dexamethasone. Significant increase in TAT activity was observed from 2 h after glucocorticoid administration and peaked at 4 h, and declined gradually thereafter. Cycloheximide even at high doses of 100 and 300 mg/kg failed to affect the increase in TAT activity by dexamethasone. On the contrary, actinomycin D at doses of 1 and 10 mg/kg abrogated the TAT activity increase by dexamethasone almost completely. Treatment with 1 mg/kg of actinomycin D, however, failed to affect the inhibition of PCA and histamine-induced cutaneous reaction by dexamethasone. These results suggest that glucocorticoids exhibit their inhibitory action of PCA and chemical mediator-induced cutaneous reactions in mice through a mechanism resistant to actinomycin D treatment.

Mechanisms for Glucocorticoid Inhibition of Immediate Hypersensitivity Reactions in Rats

The inhibitory mechanisms of immediate hypersensitivity reactions by glucocorticoid (GC) were studied in rats. Homologous passive cutaneous anaphylaxis (PCA) mediated by IgE antibodies and cutaneous reactions caused by histamine, serotonin and leukotriene C4 were elicited at the same time in the same rats. Three kinds of GC, hydrocortisone, prednisolone and dexamethasone, inhibited all these reactions significantly. Although mediator-induced cutaneous reactions were inhibited transiently around 2 hours after GC administration, inhibition of PCA was more potent and lasted longer. A time lag seemed to be essential for both inhibitions. IgE antibody-mediated histamine release in vivo in the rat peritoneal cavity was also inhibited by GC administration significantly, and the inhibition was long lasting when compared to those of the mediator-induced cutaneous reactions. Tyrosine aminotransferase (TAT) activity in the rat liver increased significantly by GC administration, and the increased TAT activity was completely abrogated by simultaneous administration of 5 mg/kg of cycloheximide (CH). In the same experimental condition, although inhibition of histamine-induced cutaneous reaction by GC was completely abrogated, the inhibition of PCA elicited at the same time in the same rats was only partially attenuated. Furthermore, the same dose of CH little affected the dexamethasone inhibition of histamine release in the rat peritoneal cavity, although the increase of TAT activity in the liver of the same rats was completely abrogated. These results demonstrate that PCA is inhibited by GC through at least 2 mechanisms, inhibition of mediator release from mast cells and non-specific inhibition of vascular permeability increase caused by released mediators. Although the latter action of GC is dependent upon protein synthesis, the former seems to be mediated by a unique mechanism independent of protein synthesis.

Effect of ciprofibrate, bezafibrate, and LY171883 on peroxisomal β-oxidation in cultured rat, dog, and rhesus monkey hepatocytes

Cultured rat hepatocytes have been used extensively to study the mechanisms of chemically induced peroxisome proliferation. Hepatocytes from nonrodent species have been used on a limited scale to study interspecies differences in the response. Because of their importance in pharmaceutical safety assessment, we have developed a model to study the response of beagle dog and rhesus monkey hepatocytes to peroxisome proliferators. Treatment of the hepatocytes with peroxisome proliferators was begun after 20 hr in culture and continued for 72 hr. Untreated rat, dog, and monkey hepatocytes retained 62, 42, and 43% of their initial (20 hr) peroxisomal β-oxidation activity throughout 92 hr of culture. Ciprofibrate, bezafibrate, and LY171883 caused a dose-related increase in β-oxidation in rat hepatocytes to a maximum of 10-, 8-, and 5-fold, respectively. In dog and monkey hepatocytes the increases in β-oxidation were less than 2-fold. Peroxisome morphology in dog and monkey hepatocytes appeared to be unchanged by the drugs. Morphometric analysis in monkey hepatocytes showed no increase in peroxisome volume fraction in response to the chemicals. Treatment of dog and monkey hepatocytes with dexamethasone and glucagon during the final 24 hr in culture caused a 4- to 6-fold increase in tyrosine aminotransferase activity. This induction is characteristic of the in vivo response. The small increase in β-oxidation reflects the relative insensitivity of the dog and monkey liver to peroxisome proliferators in vivo rather than a loss of sensitivity during culture. Cultured hepatocytes from beagle dog and rhesus monkey may provide a model for studying the mechanisms underlying the interspecies differences. Such information would help clarify the relevance of rodent data in human risk assessment.

Insulin-mediated regulation of tyrosine aminotransferase in rat hepatoma cells: Inhibition of transcription and inhibition of enzyme degradation

Insulin induces the enzyme tyrosine aminotransferase (TAT) in Reuber H-35 rat hepatoma cells. A clone of these cells (KRC-7) was used to study the relationship between changes in enzyme activity and hybridizable mRNA, and rates of transcription for TAT in response to insulin. Our results indicate that enzyme activity is inducible by insulin in the presence of an inhibitor of RNA synthesis, suggesting that insulin functions post-transcriptionally to increase enzyme activity. Unexpectedly, insulin causes a decrease in the level of hybridizable TAT mRNA. Glucocorticoids cause an increase in TAT mRNA and insulin inhibits this increase when added either subsequent to or simultaneous with the addition of this agonist. Transcriptional runoffs demonstrate that insulin inhibits transcription of TAT to account for the aforementioned decrease in hybridizable mRNA. To examine the possibility that a post-translational mechanism is responsible for the increase in TAT activity caused by insulin, the rate of degradation of TAT protein was measured using polyclonal antibody. These experiments indicate that the rate of degradation of TAT is decreased about twofold in the presence of insulin, which suggests that part of the observed increase in TAT activity is due to selective post-translational stabilization of TAT. Therefore, insulin regulates TAT in KRC-7 cells by both transcriptional and post-translational mechanisms, the latter being responsible for the increase in activity.

The increase in hepatic tyrosine aminotransferase activity by ethanol administration involves an acceleration of enzyme synthesis

The present study was conducted to examine the nature of the increase in tyrosine aminotransferase (TAT) activity by acute ethanol administration. A significant rise in aminotransferase activity was observed as early as 1 hr after intact rats were gavaged with ethanol. Ethanol administration also increased TAT activity in adrenalectomized rats. Inhibition of ethanol metabolism by pyrazole administration had no effect on the ethanol-induced increase in TAT activity. Immunochemical analyses revealed that the enhancement of TAT activity in ethanol-fed rats correlated with an increase in aminotransferase protein. Measurement of the rate of TAT synthesis showed that in ethanol-fed rats, [3H]leucine was incorporated into the aminotransferase protein at a higher rate than in controls by a factor which was similar to the enhancement in enzyme activity. Our findings indicate that an acceleration of TAT synthesis fully accounts for the increase in TAT activity during the early stage of enzyme induction. TAT induction by ethanol administration is not dependent upon an increase in adrenal corticosteroid production, nor does it require ethanol metabolism.

The effect of sodium butyrate on tyrosine aminotransferase induction in primary cultures of normal adult rat hepatocytes

Treatment of primary cultures of adult rat hepatocytes with 5 m m butyrate inhibited the spontaneous decrease in basal activity and mRNA levels of tyrosine aminotransferase (TAT) that occurred during culture (Staecker et al., submitted). We report here that butyrate treatment of primary cultures of rat hepatocytes initially inhibited the induction of TAT. This inhibition was followed by a period of accelerated TAT induction. TAT induction in butyrate-treated primary cultures of adult rat hepatocytes occurred only after metabolism of butyrate by the cultured hepatocytes. The accelerated induction of TAT in hepatocyte cultures treated with sodium butyrate was reflected by increased TAT activity and mRNA levels. Cultured hepatocytes rapidly metabolized butyrate, but the addition of more butyrate into cultures after its initial metabolism resulted in a rapid reduction in TAT activity. These findings indicate that butyrate treatment can affect the expression of TAT in primary hepatocyte cultures in both a positive (increased basal TAT expression) and a negative (inhibition of the induced expression of TAT) manner.

Transcriptional and posttranscriptional regulation of tyrosine aminotransferase by insulin in rat hepatoma cells.

The molecular mechanisms of induction of tyrosine aminotransferase (TAT) by insulin were studied in the well-differentiated rat hepatoma cell line Fao. Incubation of Fao cells with insulin resulted in a 2-fold increase in TAT activity and TAT mRNA measured by Northern blot analysis with an oligonucleotide probe to the 5' end of the gene. The effect of insulin on TAT activity had a lag period of 30-60 min and was maximal within 4-5 h. The insulin effect on TAT mRNA was rapid, half-maximal after 15 min, and complete within 1-2 h. Insulin dose-response curves for stimulation of TAT activity and TAT mRNA were almost identical. TAT mRNA levels and enzyme activity were also stimulated by anti-insulin receptor antibodies and dexamethasone but not by wheat germ agglutinin, concanavalin A, or phytohemagglutin. The effect of insulin on the TAT gene was further investigated by measuring the relative rate of transcription in isolated nuclei using genomic TAT clones. Insulin produced a 1.5-1.7-fold increase in the production of TAT RNA transcripts. Dexamethasone induced both TAT activity and TAT mRNA to a comparable extent. In the presence of dexamethasone, insulin produced an additional 2-fold stimulation of TAT activity but had no additional effect on the abundance of TAT mRNA. These data provide direct evidence that insulin can increase TAT activity by at least two distinct mechanisms: insulin alone appears to increase TAT activity and TAT mRNA due to a stimulation of the TAT gene transcription rate; while in the presence of glucocorticoids, insulin increases TAT activity but not TAT mRNA, suggesting an insulin effect at the posttranscriptional level.

Binding of ester and amide epimers of 20ξ-dihydroprednisolonic acid to cytosol receptors and their acute pharmacological activities in rats

The competitive binding of two new classes of anti-inflammatory steroids, the esters and amides derived from the epimers of 20ξ -dihydroprednisolonic acid, to cytosol receptors from rat liver and thymus was studied. The relative inhibition of [ 3H]dexamethasone binding by the steroid derivatives was the same, irrespective of the receptor source, with the following order: dexamethasone > prednisolone > methyl 17,20α-acetonidodihydroprednisolonate > methyl 17,20β-acetonidodihydroprednisolonate > N-propyl 20α-dihydroprednisolonamide > methyl 20α-dihydroprednisolonate > methyl 20β-dihydroprednisolonate > N-propyl 20β-dihydroprednisolonamide. The α-epimer of the steroids always showed a higher binding affinity than the corresponding β-epimer. In an acute pharmacological study, prednisolone induced the suppression of plasma corticosterone and an increase in tyrosine aminotransferase activity and glycogen content of rat liver. The esters and amides had no effect on these parameters except in the case of the acetonide derivatives of the steroid acid esters which slightly increased liver glycogen content.

Anti-inflammatory activity of the epimers of N-propyl 20ξ-dihydroprednisolonamide

The epimers of a steroid carboxamide, N-propyl 20α- and 20β -dihydroprednisolonamide, were evaluated for their local and systemic effects on granuloma formation, pituitary-adrenal function and liver glycogen content in rats. When the carboxamides were administered locally, the 20β-epimer exhibited greater activity than the 20α-epimer in suppressing cotton pellet granuloma formation. Neither epimer had suppressive effects on thymus weight and plasma corticosterone levels at the dose level used. When the carboxamides were administered systemically, they were pharmacologically inactive. Furthermore, in acute pharmacological studies, the carboxamides neither increased tyrosine aminotransferase activity and glycogen deposition in the liver nor decreased plasma corticosterone levels and relative thymus weight.

Morphine inhibition of the insulin-inducible form of hepatic tyrosine aminotransferase

Morphine treatment in normal intact rats caused a dose-dependent increase in hepatic tyrosine aminotransferase (TAT) activity, as demonstrable up to 2 hr of exposure to the opioid alkaloid. However, such increase in TAT activity was invariably preceded by a prior decline in the enzyme level, as observed after 15 min of morphine treatment. Such an initial decline in activity was not demonstrable in diabetic animals. Further studies indicate that morphine inhibited the insulin-induced increase in TAT activity, a phenomenon which could be reversed by the opioid antagonist naloxone. The results suggest an opioid control mechanism in the regulation of the insulin-inducible form of TAT and indicate the possibilities of a trophic role of endogenous opiates in gluconeogenesis.

Induction of Ornithine Decarboxylase and Augmentation of Tyrosinc Aminotransferase Activity by N-Hydroxy-2-acetylaminofluorene and 2-Acctylaminofluorene in Rat Liver. Influence of Sex, Retinylacetate, Indomethacin, and Pentachlorophenol

IP injection in rats of 2-acetylaminofluorene (AAF) or N-hydroxy-2-acetylaminofluorene (N-OH-AAF) resulted in a transient increase of hepatic ornithine decarboxylase (ODC) and tyrosine aminotransferase (TAT) activity. Maximal activity of ODC was observed 4 hr and of TAT 3 hr after administration of either AAF or N-OH-AAF. A lag-time of 2 hr preceded the increase of ODC and TAT activity. N-OH-AAF dependent ODC induction displayed an almost linear dose-response in the dose range up to 94.1 mumol/kg bw (body weight) when the ODC activity was measured at its maximum 4 hr after administration. Elevation of the dose N-OH-AAF to 126 mol/kg bw resulted in a lower ODC induction. Administration of doses AAF to 31.4 mumol did not change ODC activity. At doses up to 126 mumol/kg bw ODC induction increased linear. TAT induction increased linear in the dose range 15.7-94.1 mumol N-OH-AAF and 31.4-94.1 mumol AAF/kg. Lowering the dose of AAF did not result in a lower ODC or TAT activity. Judged by the effects of actinomycin D or cycloheximide administered 1 hr prior to AAF or N-OH-AAF, the in vivo induction of rat liver ODC activity by AAF and N-OH-AAF appeared to be under transcriptional control, whereas augmentation of TAT activity under influence of AAF or N-OH-AAF appeared the result of (post) translational events. Induction of ODC by AAF or N-OH-AAF was not significantly changed by indomethacin, was slightly increased by pentachlorophenol (PCP) and was synergistically enhanced by retinylacetate (RA). The increase of TAT activity was stimulated by PCP and RA. The effect of PCP indicates that N-sulfonoxy-2-acetylaminofluorene is most probably not involved in the induction of ODC. AAF appeared more effective hepatic ODC inducer in females than males and moreover more effective than N-OH-AAF in females. N-OH-AAF had stronger ODC inducing capacity in males than females. Similar observations were made with respect to TAT activity. When induction of ODC is indicative for a tumor promoting property then the data presented here suggest that tumor promotion of the complete carcinogens AAF and N-OH-AAF is not mediated by N-O-sulfation; this might be due to other metabolic conversions.