CAAT-binding transcription factor(CTF) proteins are implicated in the expression of multipleforms and are probably identical to nuclear facfor-1(NF-1). In herpes simplex virus thymidinekinase gene, CTF is required not only to induce basal transcription of this gene, but also tostimlulate the transcription of this gene by thyroid hormone. Gel mobility shift assays and biotin-avidin protein-DNA binding assays were performed to investigate if the synthesis of transcription factors which bind to CCAAT sequences of the TK promoter(CTF or CTF-like factors) is stimulated by T₃ and to kdentify the CCAAT-binding proteins in GH₄C₁ cells havingendogenous thyroid hormone receptors. There are two different sized(31 and 33 kDa) CCAAT-binding proteins in GH₄C₁ cells having endogenous thyroid hormone receptors. The synthesisof these CTF-binding proteins were not affected by T₃.

Cytochrome P-450(CYP) enzymes are important in catalyzing the hiotransffrmation on manyendogeneous compounds and xenobiotics, including drugs and carcinogens. In the presentstudy, effect of nifedipine a voltage dependent calcium channel blocker on the induction ofCYP1A1 and 2B1 was investigated. Change of CYP1A1 and 2B1 activities were measuredby using specific enzyme activities and Western blot analysis. CYP1A1, as quantified by ethoxyresorufin-0-deethylase activity and Western blot with monoclonal antibody 1-7-1, increasedin liver microsome of nifedipine-treated spontaneous hypertensive rat(SHR. 30mg/kg.b.w, twicea day for 3days) but not in kidney microsome. CYP2B1, as quantified by benzyloxyresorufin-O-dealkylase activity and Western blot wit]1 monoclonal antibody 2-66-3, markedly increasedin liver microsome of nifedipine-treated SHR but slightly in kidney microsome. The resultsdemonstrate that nifedipine is a potent inducer of CYP2B1 in SHR.

Male Sprangue-Dawley rats which had been administered either ascorbic acid or DL-α-tocopherol for 4 weeks were injected intraperitoneally with a single dose of(9-¹⁴C)-2-acetylaminofluorens(AAF) 3.5hr before sacrifice. The activation and binding of a bepatocarcinogen. AAF to the nucleic acids and proteins rat liver nuclei were examined. After the precipitated DNA was enzymatically hydrolyzed and the adduct fraction was purified by Sephadex LH-20 chromatography, the individuals adduts were separated by HPLC. the liver microsomal and nuclear monooxygenase activities in AAF administered rats were increased, whereas those in ascobric acid and DL-α-tocopherol fed rats were decreased. It is suggested that microsomal and nuclear monooxygenase were essential for activated AAF to bind nucleic acid under the intracellular conditions. The inhibitory ability of ascobic acid and DL-α-tocopherol on the binding of AAF to liver nuclear DNA was most probably due to the marked inhibition of the formation of the proximate carcinogen. The protective effect of ascorbic acid and DL-α-tocopherol against the hepatocarcinogenic action of AAF may be mediated by decreased monooxygenase activities and by alteration in the binding of the esterified AAF to liver nucleic acids.

The effects of Naloxone, narcotic antagonist, pretreated with normal saline, salicylate and hydrocortisone produced by with hypovolemic shock on the rates of cytochrome components, mixed function oxidation enzyme reactions and lipid peroxidation have been determined using hepatic microsomal fractions of rats. The treatments with either of the naloxone have increased the contents of cytochrome P-450 and b_5 and NADPH- or NADH-cytochrome C reductase. But pretreated with salicylate and hydrocortisone were not change as compared to the control. The rates of O-demethylation for p-nitroanisole were decreased. Naloxone decreased the formation of lipid peroxide by pretreated salicylate and hydrocortisone. These results indicate that naloxone showed effect not only increase of blood pressure and respiration, but also cytochrome components activity, mixed function oxidation enzyme reactions and lipid peroxidation in the hepatic microsomal fractions of rats.

This study was undertaken to determine the pattern of changes in serum protein and lipoproteins in pregnancy. We have measured lipoprotein composition in age-matched non-pregnant and pregnant women(month 2, 3, 5, 9 and 10). The results are as follows: 1) Serum protein and protein content in HDL were higher and those in VLDL and LDL were lower in early pregnancy compared to non-pregnant women and all become similar to non-pregnant women in late pregnancy. 2) Serum cholesterol and cholesterol content in VLDL were higher until late preanancy and those in LDL and HDL were lower in early pregnancy and belome similar to non pregnant women in late pregnancy. 3) Serum phospholipid and phospholipid lontents in VLDL and LDL except in HDL increased during pregnancy. 4) Serum triglyceride and triglyceride contents in HDL and LDL except VLDL increased markedly during pregnancy. In conclusion the huperlipidemia of pregnancy is well recognized although the mechanisms responsible for its development remain unknown and need to be investigated further.

Binding of the hepatocarcinogen 2-acetylaminofluorene(AAF) to the DNA of rat liver homogenates was examined in vivo. Animals fed low and high concentrations vitamin A and E for 28 days and DNA isolated 2 hr following a single i.p. injection of[9-¹⁴C]acetylaminofluorene. The precipitated DNA was dissol-ved in MUP, blended and passed through an HAP column. UV-absorbing material eluted with 0.48M Nap. Following dialysis, the fraction was enzymatically hydrolyzed purified by Sephadex LH-20 chromatography and the adducts were separated by HPLC. The ability of vitamin A and E on the binding of AAF to liver DNA in vivo was markedly inhibited the formation of the proximate carcinogen, N-(deoxyguanosine-N²-yl) AAF(C-8 adduct). Vitamin A at higher concentration(2,000I.U.)exerted a stronger inhibitory effect on the formation C-8 adducts. A similar inhibition pattern was observed in higher concentration vitamin E administered rats. The data presented here demonstrated marked inhibits in the pattern of C-8 deoxyguanosine adduct formation during the premaligment phase of 2-AAF carcinogenesis.

We examined pattern of covalent modification of DNA produced in rat liver after exposure to single dose of aflatoxin B₁. DNA-bound aflatoxin B₁ adducts obtained from rat liver microsomes were hydrolyzed with weak acid to yield 2, 3-dihydro-3-hydroxy-(N⁷-guanyl) aflatoxin B₁ as major product. This adduct was derived from the aflatoxin B₁, 2, 3-dioxide and accounted for approximately 80% of the carcinogen-derived radioactivity incorporated into DNA. Acid hydrolysis of the nucleic acid-aflatoxin B₁, adducts also yielded 2,3-dihydro-2,3-dihydroxy-aflatoxin B₁ and other minor products. Vitamin A and E pretreatment of rats resulted in reduction in the level of hepatic AFB₁-DNA adducts to two-third of the control value. Therefore, administration of vitamin A and E to rats chages in AFB₁ metabolism probably decreased modification of DNA during this experiment.