David G. Kaufman

Role of Particles in Respiratory Carcinogenesis Bioassay

In animal models of lung cancer induction, metallic dust particles have been used to increase the lung retention of carcinogens and enhance tumor development. The influence of the physical characteristics of the carcinogen-dust combination on lung tumor induction was investigated in a Syrian hamster model where benzopyrene(BP)-ferric oxide suspensions were given by intratracheal instillation.

Studies on Carcinogen Binding in vitro in Isolated Hamster Tracheas

An in vitro short-term hamster tracheal organ culture system has been studied in an effort to develop an assay system capable of identifying in vivo states of increased susceptibility to respiratory carcinogens. Tracheas incubated in vitro in medium containing tritiated benzo(a)pyrene (BaP-3H) have BaP-3H bound to the DNA extracted from the tracheal epithelial cells, then purified and banded in CsCl gradients. Prior intratracheal treatment of hamsters with BaP plus Fe2O3 in vivo resulted in enhanced in vitro binding of BaP-3H to tracheal DNA. This enhanced binding is inhibited by incubation in the presence of 7,8-benzoflavone. Incubation at 0° reduced binding to a greater extent than 7,8-benzoflavone; these results suggest that binding may be composed of two components, one inhibitable by 0° temperatures but not by 7,8-benzoflavone, whereas the inducible component appears completely inhibitable by 7,8-benzoflavone. There was increased binding observed in the tracheas of vitamin A-deficient hamsters and in certain inbred hamster strains. Furthermore, there appears to be an inverse relationship between hamster age and inducible binding levels. The question of whether these results are predictive of the states of susceptibility to respiratory carcinogenesis, is being studied by comparable long-term carcinogenesis tests.

Normative and conceptual ELSI research: what it is, and why it’s important

The Ethical, Legal, and Social Implications (ELSI) Research Program of the National Human Genome Research Institute sponsors research examining ethical, legal, and social issues arising in the context of genetics/genomics. The ELSI Program endorses an understanding of research not as the sole province of empirical study, but instead as systematic study or inquiry, of which there are many types and methods. ELSI research employs both empirical and nonempirical methods. Because the latter remain relatively unfamiliar to biomedical and translational scientists, this paper seeks to elucidate the relationship between empirical and nonempirical methods in ELSI research. It pays particular attention to the research questions and methods of normative and conceptual research, which examine questions of value and meaning, respectively. To illustrate the distinct but interrelated roles of empirical and nonempirical methods in ELSI research, including normative and conceptual research, the paper demonstrates how a range of methods may be employed both to examine the evolution of the concept of incidental findings (including the recent step toward terming them ‘secondary findings’), and to address the normative question of how genomic researchers and clinicians should manage incidental such findings.

Influenza-Virus-Induced Hyperplasia of the Respiratory Tract of the Hamster

Hamster-adapted A/PR/8 influenza virus infection followed by a secondary insult consisting of 0.25 ml of 0.5% gelatin-saline instilled directly into the trachea causes epithelial hyperplasia of both the trachea and lung. The extent of the response is related to, and dependent upon, the time interval between virus infection and gelatin-saline administration; the optimal time interval is between 12 and 18 hr. The presence of hyperplasia was measured by 3H-thymidine incorporation. Hyperplasia of the trachea is first apparent 3 days after virus infection, peaks at the fourth day, and is no longer present by the twentieth day. Hyperplasia in the lung begins 4 days after virus infection, peaks at the sixth day, and is undetectable by the twentieth day. Additional studies are in progress to determine the effect of virus-induced hyperplasia on benzo(a)pyrene-ferric oxide initiated respiratory carcinogenesis.