Mutagenicity of nitrosamides and nitrosamidines in micro-organisms and plants

Use of N-methyl-N-nitrosourea treatment of fertilized egg cells for saturation mutagenesis of rice

“…The decay of nitroso compounds is catalyzed by hydroxyl ions and light, which may alter both the decay rate and the decomposition products (Neale 1976). Therefore, the pH of solution containing these nitroso compounds greatly influences the mutation frequency.…”

“…The number of mutations obtained in bacteria treated with nitroso compounds, including MNNG and MNU, is lower in stationary-phase culture than in growing culture (Adelberg et al1965, Altenbern 1966, Hince and Neale 1975, Neale 1976. In a synchronized E. coli culture, MNNG-induced mutations did not occur at random throughout the replicating chromosome but were preferentially localized in the region of the replicating fork (Cerdá Olmedo and Hanawalt 1967.…”

“…They are S N l-type monofunctional alkylating agents with a low Swain-Scott substrate constant (s) (Swain and Scott 1953) and these agents have high reactivity towards centers of low nucleophilicity such as oxygen atom sites in DNA, while S N 2-type reagents such as EMS and dimethyl sulfate, have a higher s value than S N 1 reagents and primarily attack sites of high nucleophilicity, such as ring nitrogen atom sites in DNA; they cause little alkylation at the oxygen atom sites (Neale 1976). Mutations by S N 2 reagents are induced via the error-prone pathway depend on repair system, whereas S N 1 agents are capable to induce mutations independently from error-prone repair (Neale 1976). In addition, S N 2 agents intend to cell death caused by reacting with proteins and thus the use of them are mostly limited to dry seeds with low activity of cells in plants.…”

The effect of isoprenaline on induction of tumours by methyl nitrosourea in the salivary and mammary glands of female wistar rats

“…In bacteria, this carcinogen induces mutations preferentially in the region of the chromosome replicating forks (Hince and Neale, 1975). In both rats (Kleihues, 1969) and bacteria (Neale, 1976) MNU inhibits replication of DNA synthesis, and it has been suggested that, in bacteria, this action could play a critical role in induction of proteins involved in accurate or error-prone repair of DNA damage (Neale, 1976). Nevertheless, it is apparent that the rate of DNA synthesis occurring at the time oftreatment by MNU profoundly affects the biological response of both mammalian and bacterial systems to this compound.…”

Overview: N-Nitroso Compounds as Carcinogens for Experimental Animals and Man

“…Therefore, accumulation of scientific papers in various fields on these compounds are innumerable. Teratogenicity data were reviewed by Druckrey [2] in 1973, carcinogenicity and metabolism by Magee et al [3], and mutagenicity by Montesano and Bartch [4] and by Neal [5] in 1976. More recently, the Inter national Agency for Research on Cancer, Lyon, pub lished the detailed informations on some N-nitroso compounds in volume 17 of the I ARC Monographs on the Evaluation of the Carcinogenic Risk of Chemi cals to Humans [6].…”