The occurrence of tumours in f₁, f₂ and f₃ descendants of bd rats exposed to n‐nitrosomethylurea during pregnancy

Abstract

N-nitrosomethylurea (NMU) was administered once IP at a dose of 20 mg/kg to BD female rats on the 18th day of pregnancy. The first generation descendants (F1) were mated to produce a second generation (F2), which were then mated to produce a third generation (F3). While F1 rats were exposed directly to NMU during intrauterine life, it can be reasonably excluded that F2 and F3 descendants were exposed to NMU or its metabolites. F2 and F3 rats received no other treatment and untreated rats served as controls. Kidney and nervous-tissue tumours were observed in F1 descendants and, with a lower incidence, in F2 descendants. In F3 rats, tumours of nervous tissue, but not of kidneys, were observed. These results confirm previous observations that exposure to a carcinogen during prenatal life results in an increased cancer risk which may persist for more than one generation.

Increased risk of cancer in the descendants of syrian hamsters exposed prenatally to diethylnitrosamine (DEN)

“…However, this phenomenon also seems to be a cause of growing concern about the acquired genetic risk for tumour development, since prenatal germinal tissues can simultaneously be a target of the carcinogen. Earlier experimental studies have indeed suggested that fetal germ cells in prenatal organisms may also be damaged by the transplacentally transferred carcinogens, and that such damage may be transmitted to subsequent generations (Tomatis, 1965;Tomatis and Goodall, 1969;Tanaka, 1973;Tomatis et al, 1975), thus causing neoplasms in individuals unexposed to any carcinogens. A different approach to investigating the possible consequences of carcinogen-induced germ-cell damage was the treatment of parents with a carcinogen before conception (Nomura, 1975Napalkov et a/., 1987;Turusov etal., 1992;Tomatis et al, 1990).…”

Persistence of methylated purines in the dna of various rat fetal and maternal tissues and carcinogenesis in the offspring following a single transplacental dose of N‐methyl‐N‐nitrosourea

“…Treatment of pregnant rats of various strains with N-methyl-N-nitrosourea (MNU) at the end of gestation results in a high incidence of tumors of the nervous system and, in some instances, of the kidney in offspring (Alexandrov, 1969(Alexandrov, , 1974Guthert and Warzok, 1974;Ishida et al, 1975;Tomatis et al, 1975). In the dams, the principal target is the mammary gland (Alexandrov, 1974;Tomatis ef al., 1975).…”

Effects of ethylnitrosourea administration during pregnancy on three subsequent generations of bdvi rats

“…Experimental evidence of prenatal carcinogenesis was first obtained in mice and later confirmed in guinea-pigs, rats, hamsters, pigs, rabbits and opossums. The first observation in man was reported by Herbst in 1971(Herbst et al, 1971, 1975; and since then several comprehensive reviews on the subject have been published (Tomatis, 1973;Tomatis and Mohr, 1973;Rice, 1973;Rice, 1976).…”