Everett Staffeldt

Enhancing effects of phenobarbitone and butylated hydroxytoluene on 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat

Abstract A comparison has been made between the enhancing effects of 0.05% dietary phenobarbitone and of 05% dietary butylated hydroxytoluene (BHT) on hepatic tumorigenesis in rats previously fed 2-acetylaminofluorene for a brief period. Prolonged feeding of the BHT diet produced a significant degree of enhancement which, however, was both lower in magnitude and delayed, in comparison with the enhancement produced by the phenobarbitone diet. Daily phenobarbitone injections stimulated persistent liver enlargement and a transient fourfold increase in DNA synthesis over a 5-day period. Similar treatment with BHT produced less pronounced liver enlargement after a delay of 1 day and did not stimulate DNA synthesis as did phenobarbitone. The results suggest that the dissimilar tumorigenic-enhancing abilities of BHT and phenobarbitone may result from differences in the effects of these agents on biochemical processes related to liver growth.

Effects of Glycerol on Lung and Liver Tumor Development

Mice of several strains (A/J, SWR, MaMyJ, BALB/cByJ, 129J, and C57BL/6J) were treated with the carcinogens 3-methylcholanthrene, urethane, and 4-nitroquinoline 1-oxide and then given 1 or 5% glycerol in the drinking water for up to 4 months. Effects of glycerol on lung tumor multiplicity and incidence were evaluated. The effects of glycerol were variable, and in the majority of experiments glycerol failed to enhance tumor development in mouse lung. Analysis of cell kinetics did not show a proliferative response of alveolar or bronchiolar cells to glycerol. In rats, glycerol did not enhance the appearance of putative preneoplastic liver foci, and in C3H mice it did not increase the incidence of spontaneously occurring liver tumors. It is concluded that glycerol does not increase number or incidence of lung tumors in the mouse strains used, whether the animals are pretreated with a carcinogen or not. Glycerol does not affect liver tumor development.

Some problems arising in analysis of large-scale animal irradiation experiments☆

Abstract This paper describes some of the problems that occur in experiments designed particularly to study the effects of irradiation. One of the purposes of such experiments is to provide data that allow an informed judgment on estimates of the risks for man after exposure to radiation. It is no trivial matter to establish whether exposure to agents, such as radiation, increases the probability of a tumor arising de novo or whether the effect is an advancement of the time of appearance of naturally occurring tumors. In many murine tumors, the problem of establishing which of these two possibilities is the case is increased by the high natural incidence. In order to interpret the data from carcinogenesis experiments, a knowledge of the natural history of the tumor of interest is necessary. In this paper we present data that help to elucidate the biology of lung tumors in hybrid B6CF 1 /An1 mice. The rising incidence of many tumors late in life raises the question of whether a common systemic factor is involved. In experiments with female mice, relatively low doses of radiation may sterilize the ovary with subsequent hormonal imbalances that in turn may influence the appearance of tumors in a number of hormone-influenced tissues. We have found that radiation may increase not only the age-specific rates of tumors but also the probability of the number of different tumor types. The possibility of a lack of independence of the occurrences of different tumors complicates the data analysis. To answer some of the questions we have raised, it would be of considerable help to have data on the prevalence of tumors; however, such data usually involve serial killing which is costly. We have examined the possibility of obtaining prevalence data for lung tumors by the determination of the incidence of lung tumors in mice dying from causes other than lung tumors. There appears to be no difference in the prevalence of lung tumors determined by using either this approach or serial killing.