Document K6Goprvp09KbYeG6JgM64jdK2

R&S 025353 iinm.z%n.y<i ire i&iier>ume i'as uumuuciii iui . that of thc^repair process of UV-damaged DNA, as judged from unscheduled DNA synthesis. 'J. i' V-'. ______M* H; KAPPUS, A. BUCHTER and W. BOLT: (Inst. TpxiKOi.;^tJniv:':Wilhelmstr. 56; D-7400 Tuebingen, W. Ger.) Disposition of flllil4C1^nv^chfea^ln the rati'ARCH TOXICOL 35(3): 153-162. 1976. [In Engl^ithfling!"and Ger. summ.]--Rats were exposed to the carcinogen [ 1,2-1 K^jjvmyl `chloride in afclosed system at initial concentrations below 100 ppm. When$he system was occupied by 3 rats, a half-life of vinyl chloride in the system's jatmosphere of, 1.13 0.12 h was observed. The volume of the ^ystem^w^^lO.^^l^Calciilationl'of-the clearance of vinyl chloride from the system 're^aledHhat iibout 40%;<of inspired vinyl chloride is absorbed by lung: Changes in respiration did not influence uptake of vinyl chloride. Uptake of vinyl chloride by the rats was Completely blocked by acute pretreatment1 with potent inhibitors of cytochrome P-450 dependent microsomal drug metabolism (i.e., 35 mg/kg 3-bromophenyl-4(5)-imidazole or 50 mg/kg 6-nitro-l,2,3-= benzothiadiazole in 0.6 ml/kg DMSO [dimethylsulfoxide]). A weaker inhibition was observed/after SKF 525 A [2-dimethylaminoethyl-2,2-diphenyl valerate] or5v6*^imetliyl~';l^ll^--.ben2:9t}iiadia2:ole ^(50 mg/kg in 0.6 ml/kg DMSO). Metyrapone;did rioV cause inhibition. Uptake of vinyl chloride was increased by ^Dretreatmeht; with DDT and, to a lesser extent, clotrimazol. No significant ^timulation^of ^uptake was/observed after pretreatment with phenobarbital, 3-methylchplanthrene,; rifampicin or chronic ethanol treatment. Immediately after exposure//highest''radioactivity levels were observed in liver and kidney. The radidactive metabolites of 14C-vinyl chloride were rapidly excreted, largely by the kidneys! Excretion of radioactivity in the urine was 69.4 2.6% within \" 1 *A. -.j- * , 24 h. " > ............ BIOSIS ABSTRACTS February 1977 Volume 6 No. 2 -------- 1 ** vr^-- v* --inClVt)\7Ur^Q' (ENU). A . high' proportion of/ treated mice developed tumors, particularly hepatomas,' pulmonary adenomas and carcinomas and malignant lymphomas of thymus and spleen. Liver tumors occurred most frequently in C57BL and DBAf mice, lung tumors in A mice and lymphomas in A and DBAf mice. A small proportion orC57BL: DBAf and IF mice developed tumors of the nervous system. >Xhe results are discussed with reference to the ready induction Af nervous!system/ tumors in similarly treated rats, and their relevance for numan cancer. ;1204|^^^EFFREY :Land DENNIS P. H, HSIEH. (Dep. Enviijon.