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Biomedical subjects

L M Anderson

Publications and source records attributed to L M Anderson.

At least 145 records · Page 8Linked to original sources

7,12-Dimethylbenz[alpha]anthracene-DNA adducts in cultured cells from mouse fetuses of different gestational ages.

Primary cell cultures prepared from individual litters of NIH Swiss mouse fetuses of different gestational ages were incubated with 7,12-[3H]dimethylbenz[a]anthracene (DMBA) for 24 h. Levels of binding of DMBA to DNA and the distribution of individual DMBA-deoxyribonucleoside adducts were similar in all cultures derived from fetuses of 13-15 days of gestation. However, in cells from fetuses at 17-19 days changes in DMBA-DNA binding were noted. In particular the syn bay region dihydrodiol epoxide of DMBA was responsible for a significantly greater fraction of the total DMBA-DNA binding in the cultures from the more mature fetuses.

9,10-Dimethyl-1,2-benzanthracene↗

Age, sex and late relapse in childhood lymphoblastic leukaemia.

Of 53 children with lymphoblastic leukaemia in their first remission who reached the fourth year after stopping treatment, 4 have subsequently relapsed and their cases are described. All are boys and 3 were over 10 at diagnosis despite there being only 6 such patients in the group overall. This suggests that teenage males are at special risk of late relapse and should not be considered cured on criteria applicable to younger females.

Age Factors↗

New chloramphenicol resistance locus in Bacillus subtilis.

A spontaneously occurring, noninducible, chloramphenicol-resistant mutant of Bacillus subtilis 168 has a mutation (cam-2) which maps in the ribosomal protein region of the chromosome near dal. Its presence does not confer dependence on chloramphenicol. Ribosomes of the cam-2 strain remained sensitive to chloramphenicol in in vitro protein synthesis. No chloramphenicol acetyltransferase activity could be detected.

Acetyltransferases↗

Carcinogenic effects of intracolonic benzo[a]pyrene in beta-naphthoflavone-induced mice.

Benzo[a]pyrene (BP) was administered intracolonically to ICR/Ha and C57Bl/6 female mice, 1 mg/mouse, once weekly for 14 weeks. Half of the mice received beta-naphthoflavone (beta-NF, a mixed-function oxygenase inducer) i.p. 24 h prior to the BP. No colonic neoplasms were found in any of the mice after 18 months. However, the BP treatment did cause a significant increase in numbers of primary lung tumors, forestomach papillomas, mammary carcinomas, and sarcomas in one or both strains, relative to controls, and the incidence of all of these except for the sarcomas was significantly reduced by treatment with beta-NF prior to BP. Overall, the beta-NF pretreatment reduced total incidence of neoplasms by about 30% in the ICR/Ha mice and by about 60% in the C57Bl/6 mice, and did not potentiate the action of the carcinogen in any organ.

Animals↗

Inter-investigator variability and validity of stated hydrogel lens parameters.

This study was designed to determine the variability and validity of various hydrogel contact lens parameters. The front vertex power of the contact lens was measured with the Nikon Projection Vertometer. The contact lens overall diameter, base curve, and center thickness were measured (for 59 hydrogel contact lenses) using the Hydro-Vue Soft Lens Analyzer, model 1100. These hydrogel lenses were measured by three investigators in a masked comparison. It was demonstrated that the inter-investigator variability was minimal for the measured lens parameters. However, the measured parameters differed significantly from those stated by the manufacturer.

Contact Lenses, Hydrophilic↗

Effects of polychlorinated biphenyls on lung and liver tumors initiated in suckling mice by N-nitrosodimethylamine.

A mixture of polychlorinated biphenyls (PCB), Aroclor 1254, was administered ip (500 mg/kg) to pregnant Swiss noninbred CD-1 mice on the 19th day of gestation. The suckling offspring of these mice and of controls were then treated ip with 5 mg N-nitrosodimethylamine (DMN)/kg on postnatal day 4 or day 14. The progeny were killed at 28 weeks or 18 months of age. The DMN treatment caused lung and liver tumors. Among the mice given DMN on day 14, exposure also to PCB resulted in a lower tumor incidence in some of the treatment groups. This protective action was most evident for lung tumors in both sexes at 18 months of age and for liver tumors in males at 28 weeks. However, the PCB exposure also led to significant increases in the percentage of mice with extensive DMN-initiated liver tumors at 18 months of age compared to the results obtained when only DMN was given. This effect was most pronounced in mice given DMN on postnatal day 4.

Age Factors↗

Sensitivity to carcinogenesis in nude mice: skin tumors caused by transplacental exposure to ethylnitrosourea.

Female athymic nude mice and their phenotypically normal littermates were exposed transplacentally to ethylnitrosourea. Skin tumors (papillomas and sebaceous adenomas) developed on the nude mice with an almost tenfold greater incidence than on their haired littermates. Skin tumors were also induced on nude mice but not haired controls by direct intraperitoneal treatment with ethylnitrosourea. These results indicate that nude mice have higher than normal susceptibility to carcinogenesis under some circumstances.

Adenoma↗

Isolation of an autonomously replicating DNA fragment from the region of defective bacteriophage PBSX of Bacillus subtilis.

We have isolated a 5.4-kilobase fragment of Bacillus subtilis DNA that confers the ability to replicate upon a nonreplicative plasmid. The B. subtilis 168 EcoRI fragment was ligated into the chimeric plasmid pCs540, which contains a chloramphenicol resistance determinant from the Staphylococcus aureus plasmid pC194 and an HpaII fragment from the Escherichia coli plasmid, pSC101. A recE B. subtilis derivative, strain BD224, is capable of maintaining this DNA as an autonomously replicating plasmid. In rec+ recipients, chloramphenicol-resistant transformants do not contain free plasmid. The plasmid is integrated as demonstrated by alterations in the pattern of chromosomal restriction enzyme fragments to which the plasmid hybridizes. The site of plasmid integration was mapped by PBS1-mediated transduction to the metC-PBSX region. A strain was a deletion in the region of defective bacteriophage PBSX differs in the hybridization profile obtained by probing EcoRI digests with this cloned fragment. This same deletion mutant, though proficient in normal recombinational pathways, permits autonomous replication of the plasmid apparently owing to the lack of an homologous chromosomal region with which to recombine. We believe that, like E. coli. B. subtilis contains at least one DNA fragment capable of autonomous replication when liberated from its normally integrated chromosomal site and that this cloned DNA fragment comes from the region of defective bacteriophage PBSX.

Bacillus subtilis↗

Murine colonic mucosal metabolism and cytotoxicity of benzo [alpha] pyrene.

Homogenates of colonic mucosa from seven mouse strains metabolized 14 C-benzol [alpha] pyrene (BP) to alkali-soluble and water-phase products. In those strains in which liver aryl hydrocarbon hydroxylase activity is inducible by beta-naphthoflavone (beta-NF), the C57Bl/6, BALB/c, C3H and random-bred Swiss CD-1, colonic metabolism of BP was also induced by intraperitoneal treatment with 150 mg/kg beta-NF 24 h before assay. No increase in the colonic metabolism of BP was seen after beta-NF treatment of the noninducible strains, AKR, DBA and SWR. A detailed study of the products formed was carried out with C57BL/6 male mice. High-performance liquid-chromatography analysis of the products of BP metabolism revealed that phenolic derivatives predominated, but that a small percentage of the BP was converted into the proximate carcinogen, the BP-7,8-diol. Addition of uridine 5'-diphosphoglucuronic acid to the incubation mixture caused an increase in total product formation and a shift from alkali-soluble to water-phase products. Of the water-phase products formed by beta-NF-induced colonic mucosal homogenates, about 40% were nondialyzable and associated with precipitable material. In a study of the cellular effects of BP on the colonic mucosa, intrarectal administration of 1 mg BP had a significant cytotoxic effect, as indicated by the number of pyknotic cells and 3H-thymidine-labeling index, and prior treatment with beta-NF afforded significant protection against this cytotoxicity.

Animals↗

A systems theory model for foster home studies.

Systems and communications theories applied to the delicate task of matching children with families promise an objective method for understanding the complexities of family relationships. The author shows how one agency successfully incorporated sophisticated theoretical tools into a study process evaluating the suitability of foster family applicants.

Child↗

Qualitative histological differences between transplacentally-induced lung tumors in young and aging mice.

Transplacentally-induced lung tumors arising in BALB/c mice 38-45 weeks old (late crop) were significantly larger and more invasive of the surrounding lung parenchyma than were the tumors appearing at 10-36 weeks (early crop). The late-crop tumors were also somewhat more papillary and heterogeneous. Development of the 2 crops of tumors from different cell types of origin is postulated. A specific association of lymphocytes with the pleural surfaces of some tumors was noted and this association was significantly more likely for tumors invading the parenchyma than for non-invasive ones.

Adenoma↗

Enhancement of formation of the esophageal carcinogen benzylmethylnitrosamine from its precursors by Candida albicans.

Previous studies in Linxian, an area of China with a high incidence of esophageal carcinoma, showed that fungal infections are common in the esophageal epithelium of patients with either premalignant changes or early esophageal carcinoma. Fungi of the genus Candida were the most frequent invaders. In these areas nitrate and nitrite are often present in high concentrations in drinking water and staple grains. The present studies have established the ability of Candida albicans to augment the nitrosative formation of the esophagus-specific carcinogen, benzylmethylnitrosamine (NBMA; N-nitroso-N-methylbenzylamine). Stationary C. albicans cultures, with pH held at 6.8, were incubated with the precursors of NBMA, benzylmethylamine (BMA; N-methylbenzylamine) and NaNO(2). There was a significant increase in the amount of NBMA formed in these cultures, compared to precursors-only controls. The amount of NBMA synthesized depended on fungal cell number. Exponentially growing cultures were also able to cause NBMA formation. The identity of the NBMA was confirmed by high-performance liquid chromatographic coelution with authentic NBMA in three solvent systems and by mass spectroscopy. Boiled cells and conditioned medium in which cells had been incubated were not effective in enhancing nitrosation. Cultured Candida released acidic metabolites that reduced the pH of the medium when only a low concentration of buffer was present. Spontaneous nitrosation of BMA was enhanced under these acidic conditions. Thus, C. albicans infecting the esophageal epithelium could cause local formation of NBMA by both cell-mediated catalysis and extracellular decrease in pH.

Benzylamines↗

Dimethylnitrosamine demethylase activity in fetal, suckling, and maternal mouse liver and its transplacental and transmammary induction by polychlorinated biphenyls.

Oxidative demethylation of dimethylnitrosamine (DMN) was detectable with liver homogenate preparations from fetal mice (noninbred Swiss) by day 16 of gestation; this activity increased to adult levels by postnatal day 7. Treatment of pregnant mice with a mixture of polychlorinated biphenyls (PCB's), 500 mg Aroclor 1254/kg, on the last day of gestation caused a large elevation in DMN demethylase activity in the livers of their sucklings, relative to the normal ontogenic increase, reaching a maximum at postnatal day 21. Foster nursing experiments showed that this inductive effect was due primarily to lactational delivery of the PCB]s. DMN demethylase activity in the maternal livers was significantly lower than normal during pregnancy. The mothers' livers were also less responsive to DMN demethylase induction by PCB's during the last 5 days of gestation in comparison with the response earlier in pregnancy or just after delivery. In the livers of the mothers, induced activity resulting from treatment with PCB's on day 19 of gestation reached a maximum on postnatal days 4-7 and declined to normal levels by the time of weaning.

Animals↗

N6-(Methylnitroso)adenosine: a carcinogen from a nucleic acid component.

Substituted aminopurines in nucleic acids may be nitrosated to yield carcinogenic nitrosaminopurines. To investigate this possibility, we studied the nitrosation of N6-methyladenosine under conditions simulating the gastric environment. We administered the product of this reaction, N6-(methylnitroso)adenosine (m6(NO)Ado), parenterally and orally to mice. A high incidence of thymic lymphomas, lung adenomas and some liver tumours were found in mice given m6(NO)Ado i.p. during early life. Oral administration of m6(NO)Ado to adult mice resulted in the formation of reproductive system tumours in 80% of the exposed female mice, as well as lung tumours in both sexes. The precursors of m6(NO)Ado (m6Ado and nitrite) did not elevate tumour incidence when given separately, but resulted in a significant increase in numbers of lung tumours in males when administered together. The nitrosamine base, N6-(methylnitroso)-adenine, was found to be a less potent carcinogen than m6(NO)Ado, causing lung tumours only in males and possibly a few mammary tumours in females. These results indicate the in vivo formation of a carcinogen from the precursors, N6-methyladenosine and nitrite, and show that m6(NO)Ado induces neoplasms in the reproductive system of mice, an unusual target for an N-nitroso carcinogen. Complete inhibition of nitrosaminopurine formation in vitro was obtained with ascorbic acid.

Adenosine↗

Reduction in the transplacental carcinogenic effect of methylcholanthrene in mice by prior treatment with beta-naphthoflavone.

Conversion of 14C-benzo[alpha]pyrene (BP) to alkali-soluble and water-phase products, as a measure of aryl hydrocarbon metabolism, was assayed on day 18 of gestation in the livers of pregnant C57BL/6 females and their (C57BL/6 x BALB/c)F1 fetuses. BP metabolism was inducible in both maternal and fetal livers by beta-naphthoflavone (beta-NF), injected ip on day 16 of gestation at doses of 25-130 mg/kg. At 25 and 75 mg/kg beta-NF, fetal liver metabolism of BP was induced 1.5- and 4.5-fold, respectively. The corresponding results for maternal liver indicated no effect at 25 mg/kg and 2.6-fold induction at 75 mg/kg. In a complementary carcinogenesis assay, pregnant mothers were injected ip with beta-NF (25 or 75 mg/kg) on day 15 of gestation and 3-methylcholanthrene (MC) (30 or 150 mg/kg) on day 17. Appropriate vehicle-injected control mice were also obtained. The progeny were examined for lung tumors at 28 weeks of age. The average number of lung tumors per mouse caused by 150 mg/kg MC was significantly reduced by prior treatment with beta-NF, to an extent depending on the dose of the inducer. With the 75 mg/kg dose of beta-NF, the incidence of lung tumors was reduced by half. Induction of carcinogen detoxification in maternal, fetal, and/or placental tissue is a possible mechanism by which beta-NF protected against transplacental MC tumorigenesis.

Animals↗