[Comparative study of the behavior of particulate emissions from diesel and gasoline engines in animal lungs: elimination rate and induction of benzo(a)pyrene hydroxylase and ethoxycoumarin de-ethylase]. / Vergleichende Untersuchung zum Verhalten von partikulären Diesel- und Ottomotoremissionen in Tierlungen: Eliminationsrate und Induktion der Benzo(a)pyren Hydroxylase und Ethoxycumarin Deethylase.

The emitted particulates of five diesel-engined and two gasoline-engined passenger cars were investigated for the elimination rate from hamster lungs after intratracheal instillation. In addition extracts of these particulates were studied for their influence on the mixed function oxidase activity (MFO; Benzo(a)pyrene Hydroxylase, Ethoxycoumarine Deethylase). Differences in the elimination rates of diesel soot and particulates from gasoline engines were not found. Compared with the blanc the extracts of diesel soot from two vehicles proved to give a moderate increase of the MFO activity, but a significant difference to the blanc was observed with the extracts of the gasoline engines. It should be mentioned that the effects were studied without taking into account the quantitative relations of the emissions in the ambient air. However, the amounts of particulates were extremely high in relation to the natural conditions. In the limits of our test model there is no indication of a higher toxicity of diesel-emissions.

The influence of various factors on the methylation of DNA by the oesophageal carcinogen N-nitrosomethylbenzylamine. I. The importance of alcohol.

Alcohol appears to be a predisposing factor for the high incidence of oesophageal cancer in Western France. Therefore, we have investigated the influence of ethanol on the alkylation of DNA by a carcinogen which reacts selectively with oesophageal tissue. Female Wistar rats (approximately 80 g) received a single i.v. injection of N-nitroso-[methyl-14C]benzylamine (2.5 mg/kg body weight). Four hours after injection of the carcinogen, methylation of purine bases in the DNA isolated from various organs was measured. We found that pretreating the rats with alcohol (45-69 micrograms/day/kg) for a period of 3-4 weeks leads to an enhancement of DNA methylation in the oesophagus. An increased amount of methylated purine base was also noted in lung DNA. In contrast, a reduction in the methylation rate of liver DNA was observed.

Metabolism of isomeric N-methyl-N-nitroso-(methylphenyl)-methylamines.

Isomeric N-methyl-N-nitroso-(2-, 3-, and 4-methylphenyl)-methylamines (2a, 2b and 2c, Fig. 1.) were metabolized in rats to the corresponding 2-, 3- and 4-(N-methyl-N-nitroso-aminomethyl)-benzoic acids (4-MNAB) (3a, 3b and 3c). The structures of 3b and 2c were established by synthesis and confirmed by spectroscopic evidence. Metabolic formation of 3a, 3b and 3c was determined by HPLC analysis and the time-course of 3c excretion was established. Oral intubation of the acid 3c resulted in almost quantitative excretion of this metabolite in 24 h urine thus indicating rapid detoxication. Toxicity and carcinogenicity of the isomeric 2a, 2b and 2c were compared with those of the parent N-methyl-N-nitroso-benzylamine (MNBA).

[Comparative investigations on the organotropic carcinogenic effect of different N-nitroso compounds with rat after single and chronic treatment (author's transl)]. / Vergleichende Untersuchungen über die organotrope carcinogene Wirkung verschiedener N-Nitrosoverbindungen nach einmaliger bzw. langzeitiger Applikation bei Ratten.

After the gavage of 200 mg N-nitrosodiethylamine per kg body weight only kidney tumors developed while long-term administration of 10 ppm N-nitrosodiethylamine induced esophageal tumors and hepatocellular carcinomas in female rats (SIV 50). This change of the organ-specific carcinogenic effect is not observed in experiments with N-methyl-N-nitrosobenzylamines substituted with a methyl group at the phenyl moiety. Both chronic treatment and single doses induced tumors of the esophagus and the pharynx.

Reactions of N-methyl-N-nitrosobenzylamine and related substrates with enzyme-containing cell fractions isolated from various organs of rats and mice.

Incubation of the following N-nitroso compounds with microsomes from mouse liver and an NADPH-generating system formed the products stated: benzaldehyde from N-methyl-N-nitrosobenzylamine (MNBA), acetone and formaldehyde from N-methyl-N-nitroso-(alpha-phenyl)-ethylamine (MNPE) and formaldehyde from N-methyl-N-nitroso-(2-phenyl)-isopropylamine (MNPI). Enzymes isolated from mouse liver showed more activity towards MNBA by comparison with rat liver preparations. Microsomes from the organs of female rats showed decreasing activity in the following sequence: esophagus greater than forestomach greater than liver and for female mice: liver greater than forestomach.

[Change of toxicity and carcinogenicity of n-methyl-n-nitrosobenzylamine in rats by methylsubstitution at the c-atoms adjacent to nitrogen (author's transl)]. / Veränderung der Toxicität und Carcinogenität von N-Nitroso-N-methyl-benzylamin durch Methylsubstitution an den Stickstoff benachbarten C-Atomen bei Ratten.

Substitution with a methyl group at the C-atoms adjacent to nitrogen of N-nitroso-N-methylbenzylamine (NMBA) results in a considerable reduction LD 50: N-nitroso-N-methylbenzylamine : 18 mg/kg (Druckrey et al., 1967) N-nitroso-N-methyl-(1-phenyl)-ethylamine (I) : 600 mg/kg N-nitroso-N-methyl-2-(2-phenyl)-propylamine (II) : 2100 mg/kg N-nitroso-N-ethyl-benzylamine (III) : 250 mg/kg Substitution with a methyl group at the methylene of the moiety of NMBA (NMPEA I) reduces also the carcinogenic activity, but it produces in all animals carcinomas of the oesophagus and the pharynx; the replacement of both H-atoms by methyl groups (NMPPA, II) causes under the condition chosen no development of tumors, because for the activation step no proton is available. The exchange of N-methyl by N-ethyl of NMBA (NEBA, III) however produces no change in the carcinogenicity.