Formation of mutagens in cooked foods. I. Beef.

Mutagens detectable by Salmonella typhimurium TA98, after activation by liver S-9 fraction, are formed when meat is cooked by frying, broiling and boiling. High levels of mutagenic activity are formed rapidly when frying, or more slowly during broiling. Formation of mutagens in boiled beef stock requires several days under reflux, but shows a strong concentration dependence. Time curves suggest that a period exists during which mutagens are not readily formed; however, after this period mutagen production is rapid. Hamburgers from commercial franchises were frequently mutagenically active.     

Prekallikrein-Kallikrein conversion rate as a predictor of contrast material catastrophies

An in vitro is described that attempts to detect patients with a potential for adverse systemic reactions to contrast material. This test involves measuring the rate of conversion of prekallikrein to kallikrein under certain standard conditions. In a preliminary retrospective study, the test could be used to identify such patients with a sensitivity of 88%, a specificity of 82%, and a predictive value of 79%.     

Inhibitory effects of carbon tetrachloride on dimethylnitrosamine metabolism and DNA alkylation

The effect of CCl₄ pretreatment (dose range from 0.5 to 2.0ml/kg body weight) on the pathways of dimethylnitrosamine (DMN)metabolism was investigated. The oxidative-N-demethylation bythe enzymes, DMN-demethylase I and II operating at low (4 mM)and high (200 mM) substrate concentration, respectively, wasgreatly reduced in a dose-dependent manner. In addition, thegeneration of an electrophilic intermediate capable of methylatingDNA, specifically at the N-7 and O-6 positions of guanine, wascompletely inhibited by CCl₄ (0.5 ml/kg body weight) pretreatment.When indole feeding (1% in the diet for 8 days prior to CCl₄administration) was employed as a means to enhance DMN-demethylaseactivities, it was found that the reduction of DMN-demethylaseactivities was more pronounced in these rats than in the controls.In agreement with earlier findings, 7-methylguanine and O⁶-methylguaninewere not detectable in the CCl₄ pretreated group. These resultssuggest that CCl₄ exerts a strong inhibitory action on hepaticDMN metabolism, in particular on the pathway leading to alkylationof DNA guanine. This phenomenon may explain the protective roleof CCl₄ against DMN-induced hepatotoxicity and perhaps, carcinogenicity,believed to be closely associated with the abnormal modificationsof DNA.     

Induction of cancer of the glandular stomach in rats by an extract of nitrite-treated fish

Treatment of a homogenate of the mackerel fish Sanma hirakl with nitrite at pH 3 led to the development of direct-acting mutagenic activity for Salmonella typhlmurium TA-1535. Repeated gastric intubation three times/week for 6 months of an extract containing this mutagenic activity into noninbred Wistar rats led to the induction of tumors in 8 of 12 rats 12-18 months later. Adenomas and adenocarcinomas were found in the glandular stomach, squamous cell carcinoma was observed in the forestomach, and adenocarcinoma was found in the small intestine and pancreas. Furthermore, precancerous lesions (including intestinal metaplasia and glandular hyperplasia of the glandular stomach as well as squamous cell hyperplasia) were noted in virtually all of the animals at risk. No tumors were seen in 8 control rats given the untreated fish extract alone; 1 rat had glandular hyperplasia and intestinal metaplasia. Thus a mutagenic extract of nitrite-treated fish was demonstrated to induce, in the rat glandular stomach, cancers identical to gastric cancer observed in man. Preventive m:asures, including reduction of the intake of pickled foods and the year-round daily availability of foods containing vitamin C, are discussed.     

Effect of short-term administration of N-(4-hydroxyphenyl)-all-trans-retinamide on chemically induced mammary tumors

Mammary cancer was induced in 50-day-old Sprague-Dawley rats with either 25 mg/kg body weight of N-methyl-N-nitrosourea (MNU) or 10 mg/rat of dimethylbenz(a)anthracene (DMBA). The retinoid N-(4-hydroxyphenyl)-all-trans-retinamide (RAHA) was begun in the diet (2.0 mmol/kg diet) of MNU-induced rats at 21, 48, or 52 days of age, and at 21 or 60 days of age for DMBA-induced rats. RAHA was terminated 12-17 weeks postinduction, and the animals were sacrificed at 28 weeks postinduction. Significant inhibition of tumor incidence or multiplicity was found in only one group (rats fed RAHA beginning at 48 days of age). This was not considered sufficient evidence to conclude that short-term administration of RAHA altered mammary tumor development.     

Early effects of a single intrarectal dose of 1,2-dimethylhydrazine in mice.

The early morphological and biochemical effects of intrarectally administered 1,2-dimethylhydrazine dihydrochloride on mouse colon were studied. Using [3H]thymidine autoradiography, it was found that 1,2-dimethylhydrazine dihydrochloride, 250 mg/kg decreased the number of prelabeled DNA-synthesizing cells in the distal colon as early as 30 min after instillation. During the interval from 24 hr to 2 weeks, however, the opposite effect was seen; incorporation of [3H]thymidine increased 3- to 5-fold over controls. At lower doses (0.25 to 25 mg/kg), a similar trend was observed. Histological examination showed no dramatic changes in cell structure or in tissue architecture. No changes were seen in labeling indices in the proximal colon. In the liver, cellular alterations were seen at concentrations of 25 to 250 mg/kg, particularly in the centrolobular region. These changes were evident at 2 hr and disappeared by 4 hr. The kidney was unaffected by 1,2-dimethylhydrazine dihydrochloride at any concentration. Our results suggest that enzymes capable of activating 1,2-dimethylhydrazine dihydrochloride are located within the mucosal cells of the distal colon.     

Excel97在药物分析中的应用

目的：在药物分析中,电子表格软件ＭｉｃｒｏｓｏｆｔＥｘｃｅ１９７ｆｏｒ Ｗｉｎｄｏｗｓ。方法：利用Ｅｘｃｅｌ的数据处理功能,进行药物的图表绘制、数据计算和统计处理,回归分析,特别是计算分析,并可建立分析数据库。结果和结论：Ｅｘｃｅｌ操作简单,功能强大,数据分析工作直观。     

辛伐他汀(舒降之)治疗原发性高胆固醇血症的临床比较研究

目的：比较国产辛伐他汀与进口辛伐他汀治疗原发性高胆固醇血症的疗效及安全性。方法：采用开放区组随机对照、多中心的临床设计。１５０例高胆 固醇血症病人分为验证组（５０例）、对照组（４８例）和开放组（５２例）,剂量均为每晚顿服１０ｍｇ,服药８周。结果：验证组与对照组服药前后比较,血清总胆 固醇（ＴＣ）分别降低２６．３６％和２８．３％,低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）分别降低３３．１７％和３５．５１％;验