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324. Urinary tract effects of naphthalenesulphonamides
CANCER RESEARCH
321
work raises the possibility that a variety of N-methylated carcinogens, which include the aminostilbenes, are converted in the body into N-hydroxymethyl derivatives which act as alkylating agents, in the same way as the nitrosamines and a variety of other classes of compounds displaying carcinogenic propensities. Roberts, J. J. & Warwick, G. P. (1963). Azo dye liver carcinogenesis: Reaction of hydroxymethylaminoazobenzene with nucleic acids in vitro. Nature, Lond. 197, 87. 324. Urinary tract effects of naphthalenesulphonamides The ability to induce hyperplasia (a localized cell multiplication) in the epithelium of the urinary tract of mice was studied with the following substituted naphthalenes: in position 1, -SO2NHRI, where R I = H , methyl or piperidyl; in position 4,-SO2R2, where R2=methyl, ethyl, propyl or isopropyl. The combinations R t = H with R2=methyl (I), ethyl (II) or isopropyl (III) produced compounds which were active while they were being fed but within a week of cessation of treatment the hyperplasia regressed. A similar effect was seen in the rat and possibly the rabbit but not in the guinea-pig. The remaining compounds, and a benzene analogue with R ~ = H and R2=ethyl were inactive. After 40 weeks of continuous treatment, III produced two bladder papillomas (benign tumours) and I produced bladder carcinoma in one mouse. The administration of II resulted in hyperplasia but no tumours. Accordingly the tumour-promoting action of II was tested in combination with a weak carcinogen, 2-amino-l-naphthol hydrochloride, acting as an initiator (see explanation of the two-stage mechanism of carcinogenesis (Cited in F.C.T. 1963, 1, 106). An increase in the incidence of bladder tumours was obtained with II. [Since the technique used involved implantation into the mouse bladder of.a paraffin pellet containing the initiator, control experiments should have been carried out with paraffin pellets containing no initiator. Until this is do he, the mechanism of turnout production remains somewhat uncertain. As usual, it had originally been suggested that the hyperplasia of the urinary tract was related to bladder stones or to phosphate crystals in the urine. Once again this hoary old legend was laid to rest by showing no correlation whatever between these phenomena.] Sen Gupta, K. P. (1962). Hyperplasia of urir~ary tract epithelium induced by continuous administration of sulphonamide derivatives. Brit. J. Cancer 16, 1 I0. Sen Gupta, K. P. (1962). Tumour-promoting action of 4-ethylsulphonyl-naphthalene-lsulphonamide. Nature, Lond. 194, 1185. 325. Carcinogens in sea plants Continuing their investigations on the occurrence of carcinogenic substances in water and soil the authors turned their attention to the phytoplankton (1) (minute plants which float or drift near the'surface of seas and lakes) taken from the Bodensee in Germany. Paper chromatography of dried benzene extracts of I revealed the presence of a number of aromatic and polycyclic hydrocarbons, half of which are known carcinogens. Many of these compounds were further characterized by means of ultraviolet absorption and spectrofluorimetric techniques. The concentrations of these compounds were determined and are expressed in ppm of dried I as follows: fluoranthene (300); 1,2-benzanthracene (20); 3,4benzpyrene (2); 1,-12 benzfluoranthene (100) and 3,4-, 10,11-, and 11,12-benzfluoranthene (100, 50 and 20 respectively). Six unidentified fluorescing polycyclic hydrocarbons at concentrations of 10, 50, 20, 20, 20, and 2 ppm were also present in dried I. [The phytoplankton are of great ecological and economic importance providing food for fish and whales. The carcinogenic hydrocarbons found in I are therefore likely to make their way into fish and whales and possibly eventually to man. Further experiments must be undertaken to elucidate the sources of these substances in I.]
321
work raises the possibility that a variety of N-methylated carcinogens, which include the aminostilbenes, are converted in the body into N-hydroxymethyl derivatives which act as alkylating agents, in the same way as the nitrosamines and a variety of other classes of compounds displaying carcinogenic propensities. Roberts, J. J. & Warwick, G. P. (1963). Azo dye liver carcinogenesis: Reaction of hydroxymethylaminoazobenzene with nucleic acids in vitro. Nature, Lond. 197, 87. 324. Urinary tract effects of naphthalenesulphonamides The ability to induce hyperplasia (a localized cell multiplication) in the epithelium of the urinary tract of mice was studied with the following substituted naphthalenes: in position 1, -SO2NHRI, where R I = H , methyl or piperidyl; in position 4,-SO2R2, where R2=methyl, ethyl, propyl or isopropyl. The combinations R t = H with R2=methyl (I), ethyl (II) or isopropyl (III) produced compounds which were active while they were being fed but within a week of cessation of treatment the hyperplasia regressed. A similar effect was seen in the rat and possibly the rabbit but not in the guinea-pig. The remaining compounds, and a benzene analogue with R ~ = H and R2=ethyl were inactive. After 40 weeks of continuous treatment, III produced two bladder papillomas (benign tumours) and I produced bladder carcinoma in one mouse. The administration of II resulted in hyperplasia but no tumours. Accordingly the tumour-promoting action of II was tested in combination with a weak carcinogen, 2-amino-l-naphthol hydrochloride, acting as an initiator (see explanation of the two-stage mechanism of carcinogenesis (Cited in F.C.T. 1963, 1, 106). An increase in the incidence of bladder tumours was obtained with II. [Since the technique used involved implantation into the mouse bladder of.a paraffin pellet containing the initiator, control experiments should have been carried out with paraffin pellets containing no initiator. Until this is do he, the mechanism of turnout production remains somewhat uncertain. As usual, it had originally been suggested that the hyperplasia of the urinary tract was related to bladder stones or to phosphate crystals in the urine. Once again this hoary old legend was laid to rest by showing no correlation whatever between these phenomena.] Sen Gupta, K. P. (1962). Hyperplasia of urir~ary tract epithelium induced by continuous administration of sulphonamide derivatives. Brit. J. Cancer 16, 1 I0. Sen Gupta, K. P. (1962). Tumour-promoting action of 4-ethylsulphonyl-naphthalene-lsulphonamide. Nature, Lond. 194, 1185. 325. Carcinogens in sea plants Continuing their investigations on the occurrence of carcinogenic substances in water and soil the authors turned their attention to the phytoplankton (1) (minute plants which float or drift near the'surface of seas and lakes) taken from the Bodensee in Germany. Paper chromatography of dried benzene extracts of I revealed the presence of a number of aromatic and polycyclic hydrocarbons, half of which are known carcinogens. Many of these compounds were further characterized by means of ultraviolet absorption and spectrofluorimetric techniques. The concentrations of these compounds were determined and are expressed in ppm of dried I as follows: fluoranthene (300); 1,2-benzanthracene (20); 3,4benzpyrene (2); 1,-12 benzfluoranthene (100) and 3,4-, 10,11-, and 11,12-benzfluoranthene (100, 50 and 20 respectively). Six unidentified fluorescing polycyclic hydrocarbons at concentrations of 10, 50, 20, 20, 20, and 2 ppm were also present in dried I. [The phytoplankton are of great ecological and economic importance providing food for fish and whales. The carcinogenic hydrocarbons found in I are therefore likely to make their way into fish and whales and possibly eventually to man. Further experiments must be undertaken to elucidate the sources of these substances in I.]