Monitoring adenovirus infections with on-line and off-line methods.

Several known process monitoring methods were tested for their efficacy in the detection of adenovirus infections. The methods that we explored include several indirect indications of viral infections, including metabolic rate analysis, secondary gauges of respiration, cell size measurement, cell number and cell viability determination, and changes in capacitance. Direct indications of the adenovirus infection were also applied, including total viral particle and infectious particle measurements, as well as a flow cytometry method for detecting infected cells. All of the methods tested in the study provide some positive indication of an adenovirus infection. Many of the methods require repeated sampling, which may limit their utility in a manufacturing process. All of the indirect measures of viral infection may be limited by the fact that they do not uniquely identify an infection. The simplest monitoring methods appear to be detection of changes in respiration or the capacitance of the culture, both of which seem to provide a clear indication of an infection. Further work will be required to demonstrate that these indications are characteristic of only a successful and productive adenovirus infection.

A probit analysis program for the personal computer.

Application software for economical and convenient calculation of median effective doses, confidence limits, potency ratios and slopes of quantal dose-response curves using a microcomputer is presented. The PASCAL language program is stored on diskette and it is compatible with many commercially available microcomputer systems. The program will simultaneously calculate the parameters for up to 20 different treatments and a total of 100 doses. Comparisons between the results of calculations of the LD50 of thiopental in mice using the PASCAL program, a modem-accessed commercially available probit analysis program and three, widely accepted manual calculation methods are made. The results of calculations of parallelism and the potency ratio between thiopental and phenobarbital-induced death in mice are shown.

Mutagenicity of nitrofluoranthenes, 3-aminofluoranthene and 1-nitropyrene in Chinese hamster V79 cells.

1-Nitropyrene (1-NO2Py), 3-nitrofluoranthene (3-NO2Ft), 3-aminofluoranthene (3-NH2Ft) and 8-nitrofluoranthene (8-NO2Ft) were tested for mutagenicity in cultured Chinese hamster V79 cells. Mutations at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) gene locus were quantified. 1-NO2Py had marginal direct-acting mutagenicity which was enhanced by a mixture of Aroclor 1254- and 1242-induced liver homogenates (S9) in the treatment medium. 1-NO2Py was more mutagenic with S9 activation than 3-NO2Ft, 3-NH2Ft or 8-NO2Ft. However, 8-NO2Ft, 3-NO2Ft and 3-NH2Ft were more mutagenic than 1-NO2Py when a post-microsomal liver supernatant (S100) was used for metabolic activation. The results of these investigations strongly support activation of some nitrated polycyclic aromatic hydrocarbons to proximate mutagens by a sequence of reductions and possible formation of polycyclic aromatic hydroxylamines.