Zeitschrift fur Krebsforschung und klinische Onkologie. Cancer research and clinical oncology最新文献

After subcutaneous administration of dipropylnitrosamine (DPN) to Syrian hamsters, gas-liquid chromatographic analysis of the 16-h urine revealed the DPN metabolites, 2-hydroxypropyl-, 2-oxopropyl-, and methylpropylnitrosamines. In a related series of experiments, hamsters received equimolar doses of the above compounds and of N-nitrosobis(2-hydroxypropyl)-amine (BHP) and 2,2'-dimethyldipropylnitrosamine (DMDPN). The metabolites as well as BHP and DMDPN had a weaker effect than did DPN on the rate and/or latency of respiratory tumors. In the respiratory tract, the segmental tumor distribution and histological types varied according to the compounds. The metabolites of DPN induced additional tumors in the digestive tract. These experiments do not support the concept that the beta-oxidized metabolites of DPN are the proximate carcinogens of the parent compound.

1-Acetoxypropylpropylnitrosamine (1-APPN) was synthesized and its biological effect examined in Syrian hamsters after subcutaneous (s.c.) administration. 1-APPN induced mesenchymal and epithelial neoplasms at the injection sites, as well as epithelial tumors in remote organs. Local neoplasms were a.c. sarcomas, mammary adenocarcinomas and Schwannomas, whereas tumors of the respiratory tract (papillary polyps, papillomas, adenomas, epidermoid carcinomas, and adenocarcinomas) were attributed to a systemic effect as were pancreas duct tumors. Neoplasms which originated in the upper digestive and genital tracts of females (papillomas, epidermoid carcinomas) may be related to a systemic and local effect of 1-APPN.

Results from a dose-response study in rats are reported, in which daily oral doses of 10, 3, 1, and 0.3 mg/kg bodyweight/day respectively were administered. The three highest dose levels resulted in incidences of liver cancer of 46, 84, and 32% respectively. In the lowest dose group (0.3 mg/kg/day) no statistically significant increase in tumor rate compared to untreated controls was found.

A previously reported experimental technique for estimation of the per-operative intravascular tumor cell shedding was further studied. A significant increased tumor cell shedding was found in rats after tumor biopsy compared with animals operatively prepared for such a biopsy. An attempt was made to estimate the number of intravascularly shedded vital tumor cells under biopsy.

Within a collective of 1431 salivavry gland tumors of the salivary gland register (1965--1976) an observation has been done, which has been classified as a "carcinoma in a papillary cystadenolymphoma". Corresponding to the "carcinoma in a pleomorphous adenoma" of the WHO-classification of salivary gland tumors the terminus "carcinoma in a cystadenolymphoma" is further defined. 6 additional cases from the literature are reviewed. The possible role of epithelial metaplasia and of a proceding radiation in the development of carcinomas in cystadenolymphomas are discussed. The following other tumors have to be differentiated from a carcinoma in a cystadenolymphoma: Metastases of other tumors beyond a cystadenolymphoma; malignant lymphoepithelial lesions (predominantly malignant lymphomas in a preexisting immune-sialadenitis of the myoepithelial sialadenitis type; rare carcinomas), and lymphoepitheliomas.

The carcinogenicity of sodium nitrite and methylguanidine singly and together were examined in rats. A hepatocellular carcinoma, a hemangiosarcoma and a spindle cell sarcoma were found in 3 of 15 rats fed continuously on pellet diet containing 0.16% sodium nitrite and 0.16% methylguanidine. Hemangiomas and bile duct adenomas of the liver were also found in 6 and 8, respectively, of the 15 rats in this group. Hemangiomas and bile ducts adenomas of the liver were found in 2 and 3, respectively, of the 4 rats fed on pellet diet containing 0.16% sodium nitrite. Only 1 of 5 rats fed on pellet diet containing 0.16% methylguanidine developed a hemangioma. No tumor was found in the control group. All the tumors were found in rats that survived for over 12 months. No significant changes were detected in the esophagus or stomach.

Supercoiled DNA duplexes of phages phiX 174 and PM2 were treated in aqueous solution at neutral pH with ultimate and proximate carcinogens. Subsequently, the carcinogen-treated phage DNAs were subjected to velocity sedimentation in neutral and alkaline sucrose to quantitative introduction of single strand breaks. Reaction of phage DNA with the ultimate carcinogens N-methyl-N-nitrosourea (MeNOUr), N-ethyl-N-nitrosourea (EtNOUr), 7-bromomethyl-benza[a]-anthracene, N-acetoxy-2-acetylaminofluorene [(Ac)2ONFln] and K-region oxides for short periods followed by sedimentation in neutral sucrose gradients led to very few breaks. Incubation with the proximate carcinogens N-hydroxy-2-acetylaminofluorene, 2-acetylaminofluorene, 7-methyl-, and 7,12-dimethyl-benza[a]anthracene did not result in breaks. However, when the phage DNAs were reacted with the ultimate carcinogens under the same conditions but subsequently alkali-denatured and sedimented in alkaline sucrose gradients, single strand breaks were readily introduced. Incubation with the proximate carcinogens followed by alkali denaturation and sedimentation in alkaline sucrose showed that only 7,12-dimethyl-benz[a]anthracene and, to a minor extent, 7-methyl-benz[]anthracene caused alkali-inducible breaks. The ability of N-methyl-N'-nitro-N-nitrosoguanidine to effect breakdown of superhelical phage DNA in alkali was found enhanced in the presence of N-acetyl-cysteine.

Nitrosopiperidine (NP) was found in Syrian hamsters quantitatively in the maternal blood for more than 8 h after subcutaneous injection, whereas it disappeared from placenta, fetus and amniotic fluid within the same time period. For N6MI, only traces were seen after 2 h in the same tissues. The long-term transplacental effect of a single dose of NP was weak, as demonstrated by a low respiratory tract tumor incidence (P-generation: 54%, F1- generation: 4%). Some tumors occurring in the digestive tract of exposed young were not found in their mothers and not commonly observed in controls. These tumors were considered a borderline transplacental effect. Tumors of other sites (i.e., the urogenital and genital tracts, reticuloendothelial system, endocrine organs and other tissues) corresponded in incidences to the overall fluctuations observed in this hamster colony.

In the present review we have discussed antigens, principally the CEA, which have their well defined place in the clinical management of the (malignant) diseases of the gastrointestinal tract. Though the immunological diagnosis of neoplasia is one of the research areas where the most effort and hopes are invested, it is also there, that the carcinofoetal antigens have the least usefullness at the moment. However, studies like those undertaken by Edgington and Plow are probably pointing out if not proving, that even relatively simple procedures like further purification of the antigen can improve its tumor specificity and consequently its diagnostical value (1975). Following their results the final verdict is not spoken yet as to whether CEA (or any other CFA) will even be more than an adjunctive tool in the diagnosis of malignant tumors specially those of the G.I. tract. The 0.6% of "false" positives these authors have obtained in their series with their highly purified CEA-S (against the 30% usually seen with classical CEA preparations) are provocative: one will have to discuss the question, on which grounds the decision "false positive" has been reached and whether these cases are not simply "clinically silent", hence true positive observations. The problem then would be shifted away from the CEA test (or any other CFA test) toward the improvement of all the other conventionally employed diagnostical measurements, which should allow the early confirmation--and localization--of a beginning neoplasia, which has been screened out by an immunological test. Until this is not warranted, the CEA test has its definite place and vocation at the present time in the follow-up of the treated cancer patient, whatever therapy he has received.

The aliphatic nitrosamines dimethylnitrosamine (DMN), diethylnitrosamine (DEN), dipropylnitrosamine (DPN), and dibutylnitrosamine (DBN) reached fetal tissue in quantitatively measurable amounts after subcutaneous administration to pregnant Syrian hamsters. The compounds were present for at least 2 h in maternal blood, placenta, fetus, and amniotic fluid; DBN was still measurable after 6 h. Only a weak or borderline transplacental effect was seen when incidences and latencies of neoplasms in the respiratory and digestive tracts of the F1-generation were compared with those of the P-generation after exposure to a single dose of DMN or DPN. However, some tumor types occurred at relatively high rates in the young, but were seen only occcasionally in their mothers or in this hamster colony in general.