ANALYSIS OF ESTROGEN-INDUCED ANEUPLOIDY AND CHROMOSOME DISPLACEMENT

Diethylstilbestrol (DES) is a known human carcinogen and teratogen whose mechanism of action remains undetermined. As essentially diploid Chinese hamster cell line (Don) was used to test diethylstilbestrol (DES), dienestrol, hexestrol and the naturally occurring estrogens, estradiol and estriol for their ability to cause metaphase arrest and to induce aneuploidy. These compounds arrest mitosis within a narrow range of high concentrations and induce aneuploidy in recovering cell populations. DES was the most effective arrestant on a comparative molar basis. Estradiol and estriol were less potent as arrestants but were effective inducers of aneuploidy. Aneuploidy was induced in a non-random manner. The smallest chromosomes were most frequently recorded in aneuploid cells. Using anti-tubulin antibody and indirect immunofluorescence, it was found that DES inhibits bi-polar spindle assembly and disrupts the cytoplasmic microtubule complex (CMTC). Estradiol arrests mitosis in a manner that allows spindle assembly. Estradiol has no apparent effect on the CMTC. The naturally occurring estrogens caused chromosome displacement during mitotic arrest. Electron microscopy confirmed that the displaced chromosomes appeared at the polar regions of arrested cells. The arresting effect of estradiol, and to some extent DES, was reduced by the addition of dibutyryl cyclic adenosine monophosphate (db-cAMP). Aneuploidy induction by DES and similar compounds may be related to their carcinogenic and/or teratogenic potential. ^

THE EVALUATION OF PUBLIC HEALTH COMPONENTS OF INTERNATIONAL DISASTER RELIEF OPERATIONS: INDOCHINESE REFUGEES IN THAILAND, 1979-1982

Refugee populations suffer poor health status and yet the activities of refugee relief agencies in the public health sector have not been subjected previously to comprehensive evaluation. The purpose of this study was to examine the effectiveness and cost of the major public health service inputs of the international relief operation for Indochinese refugees in Thailand coordinated by the United Nations High Commissioner for Refugees (UNHCR). The investigator collected data from surveillance reports and agency records pertaining to 11 old refugee camps administered by the Government of Thailand Ministry of Interior (MOI) since an earlier refugee influx, and five new Khmer holding centers administered directly by UNHCR, from November, 1979, to March, 1982.^ Generous international funding permitted UNHCR to maintain a higher level of public health service inputs than refugees usually enjoyed in their countries of origin or than Thais around them enjoyed. Annual per capita expenditure for public health inputs averaged approximately US$151. Indochinese refugees in Thailand, for the most part, had access to adequate general food rations, to supplementary feeding programs, and to preventive health measures, and enjoyed high-quality medical services. Old refugee camps administered by MOI consistently received public health inputs of lower quantity and quality compared with new UNHCR-administered holding centers, despite comparable per capita expenditure after both types of camps had stabilized (static phase).^ Mortality and morbidity rates among new Khmer refugees were catastrophic during the emergency and transition phases of camp development. Health status in the refugee population during the static phase, however, was similar to, or better than, health status in the refugees' countries of origin or the Thai communities surrounding the camps. During the static phase, mortality and morbidity generally remained stable at roughly the same low levels in both types of camps.^ Furthermore, the results of multiple regression analyses demonstrated that combined public health inputs accounted for from one to 23 per cent of the variation in refugee mortality and morbidity. The direction of associations between some public health inputs and specific health outcome variables demonstrated no clear pattern. ^