Effect of aging and interval between primary and secondary treatment in carcinogenesis induced by neonatal exposure to 5-bromodeoxyuridine and subsequent administration of N-nitrosomethylurea in rats

The relationship between aging and carcinogenesis: a critical appraisal

“…The incidence of tumors in rats exposed to BrdUrd plus NMU at the dose of 10 mg/kg was equal to that in the rats to whom the carcinogen was injected at the age of 3 or 15 months, however, the survival of fatal tumorbearing rats was significantly decreased for the older animals. When NMU was injected at the dose of 50 mg/ kg in BrdUrd-pretreated rats, both the relative risk of tumors and the tumor-specific survival were decreased in the older animals [110]. Thus, our data have shown the long-term persistence of initiating effect of neonatal treatment with BrdUrd and provided the evidence that a sole perturbation of DNA induced by BrdUrd contributed substantially to the initiation of tumorigenesis and to the acceleration of aging.…”

“…We also evaluated the effect of DNA damages induced by neonatal exposure to BrdUrd on susceptibility of target tissues to carcinogenic effect of NMU injected at various ages [110]. Rats exposed to BrdUrd in the neonatal period received single injections of NMU at doses of 10 or 50 mg/kg at the age of 3 or 15 months.…”

“…The mathematical model of processes of aging and carcinogensesis in tissue based on the experimental data on in vivo exposure to BrdUrd [110,173,179,180] has been considered [172]. Modeling was carried out on the basis of the recurrent algorithms constructed on the stochastic equations in terms of semimartingale characteristics of the processes.…”