摘要:

AbstractA 1 mg/kg dose of the DNA alkylating agent, N‐methyl‐N‐nitrosourea (MNU), when administered on day 16 of gestation provokes a progressive retinal degeneration in CD‐1 albino mice reared under standard fluorescent lighting conditions (12 hr light : 12 hr dark); this degeneration begins at about 4 weeks post‐natally and worsens with age. It is accelerated by constant fluorescent light exposure but is retarded greatly by constant darkness, suggesting the importance of secondary insults in the post‐natal period for development of the degenerative disease. To determine whether the secondary photochemical damage might be specifically blocked, MNU‐exposed and control animals in the present study were fed an antioxidant‐enriched diet of Purina mouse chow supplemented with 0.75% butylated hydroxytoluene (BHT). A second group of MNU‐exposed and control animals were fed a non‐BHT supplemented standard Purina mouse chow diet. Systematic measurements of the number of rows of photoreceptor cell nuclei, the thickness of the inner/outer segment layer, and the thickness of the whole retina were made, to quantify any degenerative changes in animals 2, 4, 6, and 8 weeks of age. By 8 weeks, retinas of BHT‐fed, MNU‐exposed animals were significantly thicker and had more rows of photoreceptor cell nuclei than regular‐diet, MNU‐exposed animals. Moreover, the retinas of BHT‐fed animals, both for MNU‐exposed and controls, demonstrated sporadic morphologic changes in the form of circular configurations composed of ganglion cells, arcades of nuclear and plexiform layers, and, in one control animal, a hyperplastic nodule. These experiments suggested that MNU‐induced retinal degeneration may be retarded by a BHT‐enriched diet; however, continuous high doses of this compound pre‐ and post‐natally

ISSN:0270-3211    

DOI:10.1002/tcm.1770080402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractWe studied transplacental fetotoxicity, teratogenicity, and mutagenicity in Swiss Webster mice following different doses of cyclophosphamide (CP; 0, 5, 10, 15, or 20 mg/kg), a well‐known mutagen/teratogen, on day 12 of gestation. The fetal survival and weight on day 18 of gestation decreased significantly with increasing CP dose (P<0.01). The CP‐treated fetuses were also dysmorphic (e.g., shortened limbs, digital defects, cleft palate, open eyes, and hydrocephaly) and the percentage of dysmorphology increased with increasing CP doses (P<0.01). To evaluate mutagenesis, a separate group of females received 5‐bromodeoxyuridine tablet (50‐mg) implants on day 12 of gestation and a CP treatment 8 h later. Fetal liver cells were harvested 24 h post‐BrdU implant to analyze sister chromatid exchange (SCE) frequency and micronuclei. CP caused a significant increase in the SCEs per fetal liver cell from 3.4 ± 0.02 (control) to 90.0 ± 0.04 (20 mg/kg CP) (P<0.01). The increasing CP dose was also related to an increase in micronuclei. The data suggest that CP is transplacentally toxic, teratogenic, and mutagenic. Further analyses of the data suggest that the mutagenic effects of CP may in fact contribute indirectly to the CP‐related teratogenic effects. Such conclusions are based on path analysis with directional causations associated with SCEs per cell and the dysmorphic fea

ISSN:0270-3211    

DOI:10.1002/tcm.1770080403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe pyrrolizidine alkaloid heliotrine has been shown to be a powerful mutagen inDrosophila.This report has evaluated the teratogenicity of heliotrine in this organism. The alkaloid was fed to larvae and its teratogenic effects measured in various developmental stages of the insect. The pupal stage is predominantly affected. The main consequences of treatment were failed eclosions at higher alkaloid concentrations (10−4M), while lower concentrations (10−4M) permitted the eclosion of adults, but these showed abdominal abnormalities ranging from severe distortions to reduced numbers of tergite bristles.mei‐9 strains ofDrosophilawere more sensitive to the production of somatic chromosomal changes as well as the teratogenic effects of the alkaloid. These strains also showed reduced numbers of cells in histoblast nests of 6‐hour‐old prepupae. It is suggested that reduced numbers of histoblast cells in prepupae may be a consequence of genetic damage and this in turn leads to the abdominal distortions and reduced bristle numbers

ISSN:0270-3211    

DOI:10.1002/tcm.1770080404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractChlorophyllin was studied for its antimutagenic activity against aflatoxin B1inSalmonella typhimuriumstrain TA98 using the plate‐incorporation test in the presence of S9 activation. Comparative antimutagenicity between chlorophyllin and certain commonly studied antimutagens (i.e., vitamins A, C, and E, retinoic acid, and β‐carotene) was also examined. A dose‐related inhibition of aflatoxin B1mutagenicity by chlorophyllin was observed, with the mutagenicity being abolished by 860 nmole chlorophyllin per plate. The inhibitory activity of chlorophyllin occurred only when cells were treated concurrently with chlorophyllin and aflatoxin B1. The antimutagenic potency of chlorophyllin was comparable to that of vitamin A and higher than that of retinoic acid and β‐carotene. Vitamins C and E had no effect on aflatoxin B1mutagenicity under the conditions used. The results of toxicity tests and a reconstruction experiment showed that inhibition of the mutagenicity of aflatoxin B1by chlorophyllin and the other active agents was due to antimut

ISSN:0270-3211    

DOI:10.1002/tcm.1770080405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe synthesis of chemical substances has resulted in technological benefits for society and has also caused increased chemical exposures and risks of related cancers. Although progress has been made in cancer treatment, there has been little improvement in real survival time for people who develop the major forms. Therefore, the need to prevent cancer is paramount. The greatest chemical exposures and risk of associatedpreventablecancers are found in the workplace, but generally environmental exposures receive greater public attention.Chemical causes of cancer have been identified, and in some cases decades have passed before controls have been adequately instituted. Some companies show a high regard for worker health, while others may minimize or misrepresent the hazards to exposed workers. Medical personnel receive relatively little education in the recognition of industrially related diseases. Workers are often unaware of their risks or are trapped in jobs because of economic necessity, and government has been slow to regulate, in part because of lobbying efforts.Experience has shown that when chemicals are regulated relatively soon after they are identified as hazardous, lives are saved, and the industry is economically healthy; however, when regulation is delayed, thousands of people die unnecessarily, and the cost to industry and society are phenomenal. Society has the opportunity to apply the knowledge learned from these experiences as we address current problems of chemical pollution.

ISSN:0270-3211    

DOI:10.1002/tcm.1770080406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770080407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770080401

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY