Oral contraceptives containing 20 or 30 micrograms ethinylestradiol and 150 micrograms desogestrel: pharmacokinetics and pharmacodynamic parameters

The serum concentrations of ethinylestradiol (EE) and 3-keto-desogestrel (KDG) were compared during treatment with a combination of 20 micrograms EE + 150 micrograms DG (20EE/DG) or of 30 micrograms EE + 150 micrograms DG (30EE/DG). During intake of both preparations, the peak levels and the areas under the curve (AUC) of EE increased significantly by approximately 100% between days 1 and 10. In the steady state, the maximal EE levels were 75 +/- 34 pg/ml (20EE/DG) and 136 +/- 55 pg/ml (30EE/DG), and the AUC were 464 +/- 236 pg.h/ml and 840 +/- 492 pg.h/ml. The KDG levels, which were identical with both preparations, increased between days 1 and 21 by approximately 300% up to values of 4.5 +/- 1.6 ng/ml. There were large interindividual variations in the AUC of EE and KDG and no correlation between the levels of EE and KDG. On day 21 of intake of 30EE/DG, the serum concentrations of sex-hormone- and corticosteroid-binding globulin were higher by 16% and 12%, respectively than with 20EE/DG. Although the morning peak levels of cortisol did not differ, the decrease which occurred thereafter, according to the circadian rhythm, was slower with 30EE/DG. There was no relationship between the serum concentrations of EE and/or KDG and the occurrence of irregular bleedings, which was similar during treatment with both preparations. As most of the women who bled had bleedings both with 20EE/DG and 30EE/DG, an influence of predisposition can be assumed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of hexose transport in respiration deficient hamster lung fibroblasts

The transport of [3H]2-deoxy-D-glucose (2DG) and [3H]3-O-methyl-D-glucose (3-OMG) was elevated in a respiration deficient (NADH coenzyme Q [Co Q] reductase deficient) Chinese hamster lung fibroblast cell line (G14). This sugar transport increase was related to an increased Vmax for 2DG transport, 26.9 +/- 4.2 nmoles 2DG/mg protein/30 sec in the G14 cell line vs 9.5 +/- 0.6 nmoles 2DG/mg protein/30 sec in the parental V79 cell line. No differences were observed in their respective Km values for 2DG transport (3.9 +/- .6 vs. 3.0 +/- .13 mM). Factors which increase sugar transport (e.g., glucose deprivation, serum or insulin exposure) or decrease sugar transport (e.g., serum deprivation) in the parental V79 cell line had little effect on sugar transport in the G14 respiration deficient cell lines. Amino acid transport, specific 125I-insulin binding to cells, and insulin-stimulated DNA synthesis, however, were similar in both cell lines. Exposure of both cell lines to varying concentrations of cycloheximide (0.1-50 micrograms/ml) for 4 h resulted in differential effects on 2DG transport. In the parental cell line (V79) low cycloheximide concentrations resulted in decreased 2DG transport, while higher concentrations (greater than or equal to 1 microgram/ml) resulted in elevated 2DG transport. In the G14 cell line, 2DG transport decreased at all concentrations of cycloheximide (up to 50 micrograms/ml). The data indicate that the G14 mutant has been significantly and specifically affected in the expression of sugar transport activity and in the regulatory controls affecting sugar transport activity.     

Study on mutagenicity and antimutagenicity of BHT and its derivatives in a bacterial assay

The mutagenicity of butylated hydroxytoluene (BHT) and its derivatives was investigated by the Ames method using Salmonella typhimurium TA98 and TA100 with or without S9 mix. The compounds were not mutagenic in either indicator strain at concentrations ranging from 50 to 330 micrograms/plate (SQ: 3,5,3',5'-tetra-tert-butylstilbenequinone; VI-III: unidentified), 500 micrograms/plate (BE: 3,5,3',5'-tetra-tert-4,4'-dihydroxy-1,2-diphenylethylene; VI: 2,6-di-tert-butyl-4-methyl-4-tert-butylperoxy-2,5-cyclohexadienone ; VI-I: unidentified; VI-II: 3-acetyl-2,5-di-tert-cyclopenta-2,4-dienone) and 1000 micrograms/plate (BHT). The antimutagenic effects of BHT and its derivatives on mutagenesis by chemical agents were investigated in Salmonella typhimurium TA98 and TA100 and Escherichia coli WP-2 hcr-. VI-II suppressed the mutagenesis induced in TA98 and TA100 by 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide (AF-2) and that induced in WP-2 hcr- by 4-nitroquinoline-1-oxide (4NQO) without decreasing cell viability. In WP-2 hcr-, the mutagenesis induced by AF-2 and ethyl methanesulfonate was also suppressed significantly. Mutations induced by methyl methanesulfonate were slightly inhibited. However, VI-II had no effect on the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine.     

新一代糖化酶高产菌株的选育及其工业应用

【目的】建立对糖化酶生产菌种黑曲霉随机突变文库进行筛选的方法,以获得糖化酶酶活提高的突变菌株。【方法】以一株可产糖化酶的黑曲霉菌株Aspergillus niger X1为出发菌株,经硫酸二乙酯诱变获得突变文库,采用葡萄糖的结构类似物——2-脱氧葡萄糖进行筛选,并在筛选过程中逐渐提高2-脱氧葡萄糖浓度,定向选育具有2-脱氧葡萄糖抗性、高产糖化酶的突变株。【结果】获得的高产突变菌株DG36摇瓶发酵糖化酶产量比出发菌株A.niger X1提高22.2%–33.8%,经工业水平50 m~3罐发酵测试,突变株DG36发酵128 h糖化酶活可达49094 U/m L,在相同发酵时间内,其酶活较出发菌株A.niger X1提高32.8%,发酵时间缩短16.9%。【结论】本研究开发了一种以2-脱氧葡萄糖为抗性标记选育高产糖化酶突变株的方法,所得突变株DG36遗传性状稳定,与出发菌相比具有菌丝粗壮、产酶期提前、糖化酶活高、发酵时间短、有利于发酵后处理的优点。     

A case for the continued use of the intraperitoneal route of exposure

In a previous study, we demonstrated the activation of cyclophosphamide by mouse erythrocytes in a yeast test using the D7 strain of Saccharomyces cerevisiae. The present study provides further information on the ability of washed red blood cells from mice to activate 2-aminofluorene (2-AF) detected as an increase in mutation frequency of the tester strain, TA1538 (frameshift mutation) of Salmonella typhimurium. The 2-AF was tested at different concentrations (1-8 micrograms/plate) using both the liquid-suspension test and the agar-plate test. For comparison, the bioactivation of 2-AF by the hepatic postmitochondrial supernatant (S9 fraction) from Aroclor-1254-induced rats was studied. 2-AF was only found to be clearly mutagenic in the agar-plate test with both activation systems. The genetic response obtained with the erythrocytes appeared to be related to the number of cells/plate. At the lowest dose, slight differences are observed when genotoxic effects were compared to those with the S9 fraction.     

Bacterial mutagenicity of some methyl 2-cyanoacrylates and methyl 2-cyano-3-phenylacrylates

The mutagenic potential of three alkyl 2-cyanoacrylate adhesives, three commercial alkyl 2-cyanoacrylate adhesives and three methyl 2-cyano-3-phenylacrylates, was assessed using the Salmonella/microsome mutagenicity assay. Compounds were tested with and without Aroclor 1254-induced rat-liver homogenate (S9 mix). The methyl 2-cyanoacrylate adhesives were mutagenic in the standard plate test with S. typhimurium strain TA100 with and without S9 activation. Methyl 2-cyano-3-(2-bromophenyl)acrylate revealed a direct mutagenic action to S. typhimurium strain TA1535. The compounds most toxic towards the bacterium S. typhimurium, were the methyl 2-cyanoacrylate adhesives (greater than 500 micrograms/plate). All alkyl 2-cyanoacrylate adhesives were tested in a modified spot test for volatile compounds with tester strain TA100. Mutagenic and toxic effects were observed with the three methyl 2-cyanoacrylate adhesives. It can be concluded from the results that the bacterial toxicity and mutagenicity of methyl 2-cyanoacrylate adhesives may be due to the methyl 2-cyanoacrylate monomer.     

Absence of mutagenic and antimutagenic activities of fluoride in Ames salmonella assays

The mutagenicity of fluoride (as sodium fluoride, NaF) was investigated with Ames Salmonella/microsome assays in strains of TA97a, TA98, TA100, TA102 and TA1535. The concentrations of NaF tested ranged from 0.44 to 4421 micrograms/plate (0.1 to 1000 ppm F), both with and without microsome activation. In addition, the suggested antimutagenic effect of fluoride was evaluated with known mutagens at various concentrations of NaF (0.44-442.2 micrograms/plate, 0.1-100 ppm F). The data showed that NaF, in amounts from 0.44 to 442.2 micrograms/plate (0.1-100 ppm F), failed to significantly increase the number of the revertants over the number observed in the solvent (distilled deionized water) controls. Increases of NaF to, and beyond, 1100 micrograms/plate (250 ppm F) resulted in a toxic effect and a reduction of the revertants to various degrees among the strains. NaF in the presence of known mutagens did not significantly decrease the number of the revertants. The results of this study indicate that NaF does not have mutagenic or antimutagenic effects in the strains tested with Ames Salmonella assays.     

Divergent effects of 1-oleoyl-2-acetylglycerol and tumor-promoting phorbol ester on rat granulosa cell steroidogenesis in vitro

The present study was undertaken to compare the effects of diacylglycerol (synthetic 1-oleoyl-2-acetylglycerol; DG) and TPA (12-O-tetradecanoylphorbol 13-acetate) on FSH- and dibutyryl cyclic AMP ((Bu)2cAMP)-stimulated granulosa cell pregnenolone (P5), progesterone (P), and 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OH-P) secretion. Granulosa cells from immature rats pretreated with pregnant mare's serum gonadotropin (PMSG) were incubated for up to 24 h with DG (0-80 micrograms/ml) or TPA (0-80 ng/ml) in the presence or absence of FSH (150 ng/ml) or (Bu)2cAMP (1.5 mM). DG, when continually present in the culture medium (MEM), significantly stimulated basal P5 (in the presence of 25 microM cyanoketone to block further metabolism), P, and 20 alpha-OH-P secretion during 6 h and 24 h of incubation. Pretreatment with TPA for 1 h caused a substantial increase in the subsequent progestin (P + 20 alpha-OH-P) secretion. However, the phorbol ester had little or no effect on steroid secretion during 6 h of incubation, significantly inhibited the secretion of P5 and P, but stimulated 20 alpha-OH-P production in 24 h. DG and TPA exerted divergent effects on FSH- and (Bu)2cAMP-stimulated progestin secretion. Accumulation of P5 throughout the culture periods (1-24 h) was markedly increased by DG (20 micrograms/ml) but significantly inhibited in the presence of TPA (40 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential sensitivity of arachidonic acid release and 1,2-diacylglycerol formation to pertussis toxin, GDP beta S and NaF in saponin-permeabilized human platelets: possible evidence for distinct GTP-binding proteins involving phospholipase C and A2 activation

Human platelets labeled with [3H]arachidonic acid and permeabilized with saponin produced [3H]1,2-diacylglycerol (DG) by phospholipase C and released [3H]arachidonate by phospholipase A2, when activated with thrombin. Thrombin-induced arachidonate liberation was almost completely inhibited with pretreatment of pertussis toxin (10 micrograms/ml), whereas DG formation was decreased by only 20-40% in the toxin-treated platelets. Although guanosine 5'-o-(2-thiodiphosphate) (GDP beta S) suppressed arachidonate release and DG production in a dose-dependent manner, the half maximal inhibition required less than 10 microM for arachidonate release but more than 100 microM for DG production. Moreover, the dose-response effects of NaF on arachidonate release and DG formation were different. These results indicate that arachidonate release and DG formation are differently affected by these agents acting on guanine nucleotide binding proteins (G-proteins), suggesting that the distinct G proteins modulate the activity of phospholipase C and phospholipase A2.     

Activation of the human neutrophil by calcium-mobilizing ligands. II. Correlation of calcium, diacyl glycerol, and phosphatidic acid generation with superoxide anion generation

Calcium and protein kinase C (Ca2+/phospholipid-dependent enzyme) have been proposed to act as signals in triggering superoxide anion (O2-) generation by neutrophils. We have probed the adequacy and necessity of calcium and diacylglycerol (DG), activators of protein kinase C, in eliciting O2- generation and degranulation. Activation of neutrophils by the ligand 10(-7) M fMet-Leu-Phe triggered elevation of cytosolic calcium (fura-2) and a rapid, biphasic increase in labeled DG in [14C]glycerol and [3H]arachidonate prelabeled cells. Buffering of the fMet-Leu-Phe-induced elevation of cytosolic calcium with MAPTAM (a cell permeant EGTA analogue) inhibited O2- generation by 90% and degranulation by 50%, concordant with a role of calcium in signaling. However, buffering the increase in calcium also decreased DG. Since phosphatidylinositol 4,5-bisphosphate breakdown in response to fMet-Leu-Phe was not inhibited and phosphatidic acid levels were enhanced in MAPTAM pretreated cells, the removal of calcium may enhance further DG metabolism. Thus, a requirement for calcium could not be differentiated from a requirement for DG, and the profound inhibition of O2- generation in the presence of MAPTAM may reflect removal of DG. Four stimuli, fMet-Leu-Phe, 10(-7) M leukotriene B4, 100 micrograms/ml concanavalin A, and 200 nM ionomycin elevated cytosolic calcium and triggered release of specific granules, but only fMet-Leu-Phe and concanavalin A triggered substantial O2- generation. Nevertheless, all four stimuli significantly increased labeled DG. Therefore, elevated DG and elevated calcium may be necessary but do not appear adequate to elicit O2- generation. Only fMet-Leu-Phe and concanavalin A triggered generation of phosphatidic acid (PA) together with DG. Correlation of O2- generation with PA may reflect a requirement for PA per se or for a specific pool of DG that can be further metabolized to PA.     

Evaluation of diallate and triallate herbicides for genotoxic effects in a battery of in vitro and short-term in vivo tests

Commercial-grade preparations of two thiocarbamate herbicides, diallate and triallate, were evaluated for their mutagenic potential in a battery of short-term bioassays. All in vitro bioassays were performed with and without mammalian metabolic activation, and all such tests were repeated after an interval of at least 1 week. Diallate and triallate were tested in the Salmonella/microsome assay over dose ranges of 0.59 to 118.0 micrograms/plate and 6.37 to 1273 micrograms/plate, respectively. Both diallate and triallate gave positive results in S. typhimurium strains TA1535, TA98, and TA100 only in the presence of a rat-liver metabolic activation system. In Saccharomyces cerevisiae strain D7, diallate was tested at concentrations from 1.18 to 29.50 micrograms/ml, and triallate was tested at 0.955 to 9.548 micrograms/ml. Both diallate and triallate gave negative results for mitotic gene conversion, mitotic crossing-over, and reverse mutation. In the mouse lymphoma L5178Y TK+/- assay, diallate was tested at concentrations ranging from 1 to 72 micrograms/ml, and triallate was tested at 0.5 to 60 micrograms/ml. Both herbicides produced mutagenic responses in the mouse lymphoma assay in the presence of metabolic activation. In the Drosophila sex-linked recessive lethal test, flies were exposed to 0.0004% diallate and 0.001% triallate. In this assay, diallate was considered mutagenic, whereas triallate did not produce a detectable mutagenic response.     

Chemical and biological characterization of hazardous industrial waste. I. Prokaryotic bioassays and chemical analysis of a wood-preserving bottom-sediment waste

Prokaryotic bioassays, capable of detecting point mutations and lethal damage to DNA, and a GC/MS/Data System analysis were employed to evaluate the genotoxic characteristics of wood-preserving bottom sediment. Organic compounds in the waste were initially extracted with dichloromethane and then fractionated by liquid-liquid extraction into acid, base and neutral fractions. The crude extract and each of 3 subfractions were tested in 4 strains of S. typhimurium to detect point mutations and 6 strains of B subtilis to detect lethal damage to DNA. The assay using S. typhimurium responded to indirect-acting mutagens in the crude extract and all 3 primary fractions, with the maximum mutagenic response of 181 net revertants induced by the base fraction at a dose of 500 micrograms/plate. In the DNA-repair assay, the survival ratio for the repair-deficient strain recE4 when compared to the repair-proficient strain 168 wt was 0.17 and 0.09 in the acid and base fractions, respectively, at a dose of 100 micrograms/plate. Potentially genotoxic compounds identified in the waste fractions by GG/MS/DS analysis include acenaphthylene, pentachlorophenol, methyl phenanthrene, fluoranthene and pyrene. However, it appears that these identified chemicals did not contribute significantly to the observed mutagenic activity of the sample extracts.     

Absence of genotoxic activity of penbutolol in bacterial and mammalian cell screening systems

The genotoxic potential of the beta-adrenergic blocker penbutolol was assessed using the Ames and HGPRT tests, unscheduled DNA synthesis (UDS) and alkaline elution assays. In the Ames test, penbutolol was tested for cytotoxicity and genotoxic activity in concentration ranges of 0.8-500 micrograms/plate and 0.1-125 micrograms/ml in the HGPRT, UDS and alkaline elution assays. In the Ames test penbutolol showed significant toxicity above 500 micrograms/plate. In the mammalian cells (V79) used for the HGPRT test and A459 cells used for alkaline elution and UDS assays, penbutolol was cytotoxic at concentrations above 30 micrograms/ml. In another series of experiments, male Wistar rats were treated i.p. with penbutolol (1, 10 and 100 mg/kg) and after 2 h liver nuclei were isolated and formation of single DNA-strand breaks was measured. The results of the present study demonstrate the absence of genotoxic activity of penbutolol in the 5 strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537 and TA1538) and in the strain of Escherichia coli WP2 uvrA in the presence or absence of metabolic activation. In V79 cells, penbutolol showed no mutagenic effects at the HGPRT locus in the presence or absence of metabolic activation. Additionally, no significant incorporation of [3H]thymidine into the DNA in the UDS test or formation of DNA-strand breaks in the alkaline elution assay was detected in the non-toxic concentration range of penbutolol with or without metabolic activation. Furthermore, penbutolol did not cause DNA damage in liver nuclei isolated from penbutolol-treated rats.     

Genotoxicity studies on the organophosphorus insecticide chloracetophone

Chloracetophone (O,O-dimethyl-2,2,2-trichloro-1-(chloroacetoxy)phosphonate), a new insecticide of the organophosphorus group of pesticides, was tested for genotoxicity in a variety of systems with different genetic end-points and varying parameters. The test systems included 2 microbial systems, Salmonella and Aspergillus for point mutations and mitotic segregation, respectively, and human lymphocyte cultures and mammalian bone marrow cells (from rats and hamsters treated acutely and subacutely) for chromosomal aberrations and micronuclei. Chloracetophone was negative in Aspergillus at concentrations of 1-500 micrograms/ml, in human lymphocyte cultures at concentrations of 2.5-40 micrograms/ml, in rats at doses of 420-21 mg/kg b.w. and in hamsters at doses of 210-42 mg/kg b.w. for chromosomal aberrations. It did not cause any increase of micronuclei in human lymphocytes and rat bone marrow cells but did cause a significant increase in hamster bone marrow cells. Chloracetophone induced base-pair substitutions in strain TA100 of Salmonella with and without metabolic activation at a concentration range of 2000-6000 micrograms/plate.     

阿维菌素高产菌株的选育及阿维菌素B1的鉴定

自阿维链霉菌（Ｓｔｒｅｐｔｏｍｙｃｅｓ ａｖｅｒｍｉｔｉｌｉｓ ＡＴＣＣ３１２７２）中分离出了３种不同类型的菌株,其中只有产灰色了的菌株能产生阿维菌素（Ａｖｅｒｍｅｃｔｉｎｓ）,摇瓶发醇单位约１００μｇ／ｍＬ。从其菌丝体中提取纯化了阿维菌素Ｂ１晶体,其紫外吸收光谱、红外吸收光谱、核磁共振谱Ｈ－ＮＭＲ和＾１３Ｃ－ＮＭＲ）和质与国外报道的一致。Ｓａ－７６菌株又经２次亚硝基胍诱变,筛选出发酵单位２０００     

Genotoxicity tests with 6-acetyl-1,1,2,4,4,7-hexamethyltetraline and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-benzopyr an

6-Acetyl-1,1,2,4,4,7-hexamethyltetraline (AHTN) and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-ben zopyran (HHCB), synthetic fragrance ingredients, were evaluated for potential genotoxicity in a battery of short-term tests. Salmonella typhimurium/Escherichia coli plate incorporation and liquid preincubation assays were conducted on AHTN using tester strains TA97, TA98, TA100, TA102, TA1535, TA1537 and WP2 uvrA +/- S9 activation at doses from 8 to 5000 micrograms/plate. The plate incorporation mutagenicity assay was conducted on HHCB using tester strains TA98, TA100, TA1535, TA1537, TA1538 and WP2 uvrA +/- S9 activation at doses from 10 to 5000 micrograms/plate. An in vitro cytogenetics assay in Chinese hamster ovary (CHO) cells was conducted with AHTN and HHCB at three concentrations each with +/- S9 activation. In the non-activated study, the exposure/harvest periods were 4/20-, 20/20- and 44/44-h. In the S9 activated study, the exposure/harvest periods were 4/20- and 4/44-h. In vitro unscheduled DNA synthesis (UDS) assays were conducted in primary rat hepatocytes at concentrations between 0.15 and 50 micrograms/ml for AHTN and HHCB. In vivo mouse micronucleus assays were conducted with high doses of 1600 mg AHTN/kg and of 1500 mg HHCB/kg in corn oil. No positive responses were observed in any of the tests with HHCB. With AHTN, no positive responses were observed except for cells with structural aberrations in the in vitro cytogenetics assay in CHO cells with S9 activation at the treatment/harvest time of 4/20 h. In initial studies with AHTN, the high dose of 7.8 micrograms/ml showed 0.5% aberrant cells, with the mitotic index at 41% relative to vehicle control and cell growth inhibition in the range of 25-50%. Thus the genotoxicity findings with AHTN were limited to this one positive response; all other genotoxicity tests with AHTN were considered as negative. In particular, the negative finding in the in vivo assay supports AHTN as not likely to be mutagenic in mammalian systems. These considerations, along with other negative published data, lead to the conclusion that both AHTN and HHCB do not have significant potential to act as genotoxic carcinogens.     

Blood ammonia concentration in mice: normal reference values and changes during growth

To establish normal reference values of blood ammonia concentration in mice, possible factors which may affect blood ammonia determination such as age, sex, strain and sampling site of blood, were investigated by the microdiffusion method. The ammonia concentration in blood collected from the tail (mixture of venous and arterial blood) and left ventricle was significantly higher than that in venous blood collected from the orbital sinus and right auricle. Neither strain nor sex differences were observed. Blood ammonia concentration in newborn pups was 92 +/- 19 micrograms/dl immediately after birth and increased to 184 +/- 22 micrograms/dl 24 hours after birth. This increased level was maintained for a week. By 15 days, it decreased to the level at birth. Thereafter, no significant variation with age was observed. Blood ammonia concentration in mice after weaning, irrespective of age, sex and strain, varied from 38 to 123 micrograms/dl, with a mean +/- SD of 79 +/- 18 micrograms/dl.     

Serum concentrations of ethinylestradiol, 3-keto-desogestrel, SHBG, CBG and gonadotropins during treatment with a biphasic oral contraceptive containing desogestrel.

During a cross-over study, the pharmacokinetics of ethinylestradiol (EE) and 3-keto-desogestrel (KDG) were investigated on days 7 and 22 of one cycle of treatment with two biphasic formulations containing 50 micrograms EE (7 tablets) and 50 micrograms EE + 125 micrograms desogestrel (DG) (15 tablets) (50/50 EE) or 40 micrograms EE + 25 micrograms DG (7 tablets) and 30 micrograms EE + 125 micrograms DG (15 tablets) (40/30 EE). Peak serum levels and areas under the curve of EE increased significantly by 50% between days 7 and 22 of those taking 50/50 EE, while during treatment with 40/30 EE, no difference was found between days 7 and 22. Both formulations caused identical KDG levels on day 22. There were only slight differences in the effects of both preparations on sex-hormone-binding globulin (SHBG; +150 to +160%) and on corticosteroid-binding globulin (CBG; +130 to +150%) on day 7. On day 22, the changes were more pronounced with 50/50 EE (SHBG, +310%; CBG, +240%) than with 40/30 EE (SHBG, +250%; CBG, +180%). On day 22 after discontinuation of treatment, the SHBG and CBG levels were still significantly above the control values. Using both formulations, LH and FSH levels were significantly suppressed on day 22, while on day 7 no significant reduction was observed. The rise in the EE levels between days 7 and 22 of 50/50 EE intake and the time course of the EE concentrations during treatment with 40/30 EE appear to be due to an inhibition of hepatic metabolism by the contraceptive steroids, as EE is nearly exclusively bound to albumin which does not change.     

Phosphoenolpyruvate:hexose phosphotransferase systems in Lactobacillus species]

The substrate range of phosphoenolpyruvate:hexose phosphotransferase systems (hexose-PTSs) in Lactobacillus casei subsp. casei LAC3 and L. acidophilus LAC5 was examined. Strain LAC3 demonstrated PTS activities for glucose (Glc), mannose (Man), glucosamine (GcN), 2-deoxyglucose (2DG) and fructose (Fru), while strain LAC5 showed the activities only for Man and Fru. These activities were all constitutive. Growth of both strains was strongly inhibited by 2DG. 2DG-resistant mutants DG329 and DG504 were isolated, respectively, from strains LAC3 and LAC5. Mutant DG329 grown on Glc was defective in all the above-described activities observed with strain LAC3, whereas no defect in PTS activities was found in mutant DG504. Mutant DG329, however, showed some inducible activities for Man and Fru when grown on Man, Fru or Scr. These results strongly suggest that strain LAC3 has inducible PTS(s) specific for Man and/or Fru besides the well-known, broadly specific, constitutive Man-PTS, and also that strain LAC5 lacks the Man-PTS, but has other constitutive PTS(s) specific for Man and/or Fru. L. fermentum LAC12 had the Man-PTS as reported previously (Nagasaki et al., 1992), but had no inducible activities like those found in strain LAC3.     

Prophage induction and filamentation in Bacillus thuringiensis caused by the genotoxic mycotoxin aflatoxin B1

Cultures of the lysogenic strain of Bacillus thuringiensis var. tolworthi were made in the presence of various drugs. The determination of bacterial size and plaque forming units (by using an indicator strain of B. thuringiensis var. galleriae) as well as colony forming units were then performed. Treatment of lysogenic cells by aflatoxin B1: provokes the formation of elongated cells (filamentation); induces a pathway that leads to the induction of prophage. Results of the present study indicated that filament formation and bacteriophage induction are two commonplace effects that occur in virtually every member of this cellular population exposed to low doses of certain drugs such as aflatoxin B1 (10 micrograms/ml); all of which have in common the ability to produce damaging changes in DNA. The following findings support the hypothesis that error-prone repair mechanisms seem to be present in B. thuringiensis as in Escherichia coli.