Use of transgenic animals for carcinogenicity testing: considerations and implications for risk assessment

Advances in genetic engineering have created opportunities for improved understanding of the molecular basis of carcinogenesis. Through selective introduction, activation, and inactivation of specific genes, investigators can produce mice of unique genotypes and phenotypes that afford insights into the events and mechanisms responsible for tumor formation. It has been suggested that such animals might be used for routine testing of chemicals to determine their carcinogenic potential because the animals may be mechanistically relevant for understanding and predicting the human response to exposure to the chemical being tested. Before transgenic and knockout mice can be used as an adjunct or alternative to the conventional 2-year rodent bioassay, information related to the animal line to be used, study design, and data analysis and interpretation must be carefully considered. Here, we identify and review such information relative to Tg.AC and rasH2 transgenic mice and p53+/- and XPA-/- knockout mice, all of which have been proposed for use in chemical carcinogenicity testing. In addition, the implications of findings of tumors in transgenic and knockout animals when exposed to chemicals is discussed in the context of human health risk assessment.     

Effect of Various Viruses on the Responsiveness of Mouse Lymphocytes to Phytohemagglutinin Stimulation

A comparison of viral-induced unresponsiveness of phytohemagglutinin (PHA)-induced deoxyribonucleic acid (DNA) synthesis of mouse lymphocytes was made by culturing the cells under identical conditions in the presence of HEPES buffer in a humid-air atmosphere. The degree of PHA-induced DNA synthesis was found to vary, depending upon the type of ribonucleic acid or DNA virus treatment. Myxovirus, paramyxoviruses, Mengo virus, leukemic viruses, herpesvirus, and vaccinia virus caused a depression in responsiveness, whereas lactic dehydrogenase virus, adenovirus, and polyoma virus induced an increase in DNA synthesis. Inhibition of DNA synthesis was significant only if the virus was added at 0 h or within the first 12 h after PHA stimulation. Time studies indicated that leukemic and nonleukemic viruses caused similar patterns in the alteration of PHA-induced DNA synthesis.     

Competing paradigms and the St Luke's Alumnae Association minutes, 1895-1916

This study was designed to explore the relationship between the minutes of the alumnae association of a training school for nurses, from 1895 to 1916, and the occupational evolution of nursing. The members of the St Luke's Alumnae Association, even in their initial statement of purpose, consistently affirmed their ties to other nurses, thus implicitly supporting the cause of trained nursing. But the cause of trained nursing was not the same as that of professional nursing. These findings support the usefulness of the "work group" paradigm vs the paradigm of professionalization in attempting to describe accurately the occupational evolution of nursing as portrayed in the minutes.