N. Mihailovich

Carcinogenicity of diethylnitrosamine in newborn, infant, and adult mice

SummaryModifying effects of age, sex, and mouse strain on diethylnitrosamine (DEN) carcinogenesis have been investigated in C57BL/6Jx C3HeB/FeJ F1 (B6C3F1) and C3HeB/FeJxA/J F1 (C3AF1) hybrid mice. Animals each received four IP injections of 1.5 or 3.0 μg DEN/g body weight. The first injections were administered on days 1, 15, or 42 of life. Subsequent treatments were delivered at 3-, 6-, and 6-day intervals, respectively. Mice were kept under observation for the remaining life-span. DEN treatment induced tumors in liver, lungs, and forestomach in descending order of frequency. The majority of the induced liver tumors were hepatocellular carcinomas. Animals treated as newborns and infants developed significantly more liver tumors than animals that were treated as young adults. Newborn and infant females developed liver tumors at a later age (B6C3F1) and with a lower incidence (C3AF1) than similarly treated males. The B6C3F1 mice developed more hepatocellular carcinomas and a higher rate of pulmonary metastases than the C3AF1 mice. In contrast, C3AF1 mice developed lung tumors with a higher incidence and multiplicity than B6C3F1 hybrids. Forestomach tumors were observed also with a slightly but significantly higher incidence in C3AF1 mice.

Sex Hormones as Modulators of Liver Tumor Development

The induction of hepatocellular tumors depends upon the nature of the chemical agent (1), its requirement for activation to ultimate carcinogenic moiety (2), enzymatic competence of tissue(s) to activate the procarcinogen (3–5), the interaction of ultimate carcinogenic moiety with specific macromolecular site(s) (6,7), the rate of removal of the formed adduct(s) (8), the degree of macromolecular repair (9,10), caloric intake (11–13), immune competence, and hormonal environment of the host (14–17), The interplay of all these factors contribute in varying degrees to the neoplastic expression in the liver. The species, strain (18), age at treatment (19), and sex (19) of the animals may influence the degree of the agent’s activation. In addition, the age at treatment may affect the macromolecular damage-repair ratio and consequently the degree of fixation of the residual macromolecular lesion(s) (20).