785
substantially lower body-weights, probably due to their having more severe malabsorption. We suggest, therefore, that the protective effect of bran in these experiments was due at least in part to its lower energy value. Nevertheless, we would not advocate bran as a practical way of lowering energy intakes in man, since it would have to form an unacceptably large proportion of the diet to be effechad
tive. Departments of Medicine and Surgery, Bristol Royal Infirmary, Bristol BS2 8HW
K. W. HEATON R. C. N. WILLIAMSON
Ueyama et al.’ Three years ago we reported the results of a large series of experiments in which metastatic spread to lung, para-aortic node, or mesentery was detected in 5 out of 302 (1.6%) mice implanted subcutaneously with pieces from twelve types of primary carcinoma.2 Hela cells injected subcutaneously as single-cell suspensions metastasised more readily (13 out of 160 mice, 8 - 1 %) but, clearly, although xenografts of human tumours do metastasise, they do not retain the high tendency to metaslasise that is characteristic in man. It will be interesting, therefore, to see whether treatment of mice with cytosine arabinoside (cytarabine) increases true metastatic spread from unpassaged tumours implanted subcutaneously to the same extent as that found for the passaged anaplastic adenocarcinoma used by Rostrom et al.
ANTACIDS, BILE-SALTS, AND COLON CANCER SIR,-Cruse et al.’ argue that aluminium hydroxide might promote cancer of the colon by increasing the delivery of bilesalts to the large intestine. Although their study with Wistar rats did not demonstrate that the increased mortality of rats treated with dimethylhydrazine and ’Aludrox’ was due to the bile-salt-binding property of aluminium hydroxide, they’ advised caution "in the use of this agent (e.g., as an antacid) in colon cancer patients".
Among 8006 men who were examined from 1965 to 1968 in the Japan-Hawaii Cancer Study we have identified 345 who had had a gastrectomy for gastric or duodenal ulcer before their examination. Many of these men with a history of ulcers will have been former users of antacids based on aluminium hydroxide. We did not identify the men who had a history of confirmed peptic ulcer without gastrectomy at time of examination. During follow-up 4 of the gastrectomy men and 94 non-gastrectomy men have been diagnosed as having large-bowel cancer. The age-adjusted incidence-rates are 10.3 per 1000 and 12.4 per 1000, respectively, and the average person-years of follow-up in the two groups are very similar at 9.13 and 9.16. Although we do not know how many non-gastrectomy men had taken antacids frequently in the past, we do know that only 148 (2-3%) out of 6566 who responded recently to a drug questionnaire were current users of stomach medications, including antacids. Unless men with gastrectomy or peptic ulcer are protected against the development of large-bowel cancer, our data do not support the view that aluminium hydroxide can increase the risk for colorectal cancer. A. NOMURA Japan-Hawaii Cancer Study, G. N. STEMMERMANN Kuakini Medical Center, G. A. GLOBER Honolulu, Hawaii 96817, U.S.A.
National Institute for
Holly Hill, Hampstead,
Biological
Standards and Control,
A. J. GARRETT
London NW3 6RB
HAND-MIRROR CELLS IN T-CELL LYMPHOMA
SIR,-In your editorial
on
hand-mirror cells in leukaemia
(July 22, p. 195) you referred to an extensive cell-marker analysis of one case of acute lymphoblastic leukaemia by Stass et al.3 The blast cells were positive for acid phosphatase and terminal deoxynucleotidyl transferase (TdT) but T-cell-specific antigens were not investigated. We have seen a case with features very similar to that described by Stass et al. The blast SEROLOGICAL ANALYSIS OF BLAST CELLS
Microcytotoxicity test with absorbed rabbit serum as complement 4 tAbsorptions: 108 cells/ml of 1:4 diluted antiserum. $Rabbit anti-lymphocyte-serum absorbed with AB red cells, platelets, and several T lymphoid cell-lines. § Rabbit anti-A.L.L. made specific for human non-T non-B A.L.L. cells by absorptions with AB red cells, platelets, B-lymphoid cell lines, and thymocytes. Preparation and specificity of these antisera were described else*
HUMAN TUMOURS IN MICE AND RATS
SIR,-Your editorial (July 15, p. 138) and the letter from Dr Rostom and colleagues (Aug. 19, p. 428) rightly emphasise the values and some of the limitations of using xenografts of human tumours in immunodeficient animals as models for testing antitumour agents. Provided it is remembered that the greatest limitation of the system is that the tumour is a xenograft, the best model is one in which the implant is tumour tissue fresh from the patient. Passage of the tumours in vivo or in vitro often leads to alteration of certain characteristics, and in this laboratory, for example, a human melanoma in thymectomised, irradiated mice lost most of its capacity to produce melanin within 15 passages whilst still retaining a human karyotype and a rapid rate of growth. Rostom et al. seem to doubt your statement that xenografts rarely metastasise and claim that "few careful investigations of this have so far been made". They refer only to the work of 1.
Cruse, J. P., Lewin, M. R., Clark, C. G. Lancet, 1978, i, 1261.
where.s
cells had T-cell-specific antigens as well as p-glucoronidase, acid phosphatase, and TdT. The blast cells had no receptors for complemention, IgG or IgM, and no surface membrane Ig. They were recognised by several anti-human-T-cell antisera 1.
Ueyama, Y., Morita, K., Ochiai, C., Ohsawa, N., Hata, J., Tamaoki, N. Br. J. Cancer, 1978, 37, 644. 2. Franks, C. R., Boulger, L. R., Garrett, A. J., Bishop, D. Reeson, D., Perkins, F. T. Eur. J. Cancer, 1975, 11, 619. 3. Stass, S. A., Perlin, E., Jaffe, E. S.,Simon, D. R., Creegan, W. J., Robinson, J. J., Holloway, M. L., Schumacher, H. R., Am. J. Hemat. 1978, 4, 67. 4. Mittal, K. K., Mickey, M. R., Singal, D. P., Terasaki, P. I. Transplantation, 1968, 6, 913. 5. Boumsell, L., Bernard, A., Lepage, V., Lemerle, J., Dausset, J. Fed. Proc. 1978, 37, 1289.
substantially lower body-weights, probably due to their having more severe malabsorption. We suggest, therefore, that the protective effect of bran in these experiments was due at least in part to its lower energy value. Nevertheless, we would not advocate bran as a practical way of lowering energy intakes in man, since it would have to form an unacceptably large proportion of the diet to be effechad
tive. Departments of Medicine and Surgery, Bristol Royal Infirmary, Bristol BS2 8HW
K. W. HEATON R. C. N. WILLIAMSON
Ueyama et al.’ Three years ago we reported the results of a large series of experiments in which metastatic spread to lung, para-aortic node, or mesentery was detected in 5 out of 302 (1.6%) mice implanted subcutaneously with pieces from twelve types of primary carcinoma.2 Hela cells injected subcutaneously as single-cell suspensions metastasised more readily (13 out of 160 mice, 8 - 1 %) but, clearly, although xenografts of human tumours do metastasise, they do not retain the high tendency to metaslasise that is characteristic in man. It will be interesting, therefore, to see whether treatment of mice with cytosine arabinoside (cytarabine) increases true metastatic spread from unpassaged tumours implanted subcutaneously to the same extent as that found for the passaged anaplastic adenocarcinoma used by Rostrom et al.
ANTACIDS, BILE-SALTS, AND COLON CANCER SIR,-Cruse et al.’ argue that aluminium hydroxide might promote cancer of the colon by increasing the delivery of bilesalts to the large intestine. Although their study with Wistar rats did not demonstrate that the increased mortality of rats treated with dimethylhydrazine and ’Aludrox’ was due to the bile-salt-binding property of aluminium hydroxide, they’ advised caution "in the use of this agent (e.g., as an antacid) in colon cancer patients".
Among 8006 men who were examined from 1965 to 1968 in the Japan-Hawaii Cancer Study we have identified 345 who had had a gastrectomy for gastric or duodenal ulcer before their examination. Many of these men with a history of ulcers will have been former users of antacids based on aluminium hydroxide. We did not identify the men who had a history of confirmed peptic ulcer without gastrectomy at time of examination. During follow-up 4 of the gastrectomy men and 94 non-gastrectomy men have been diagnosed as having large-bowel cancer. The age-adjusted incidence-rates are 10.3 per 1000 and 12.4 per 1000, respectively, and the average person-years of follow-up in the two groups are very similar at 9.13 and 9.16. Although we do not know how many non-gastrectomy men had taken antacids frequently in the past, we do know that only 148 (2-3%) out of 6566 who responded recently to a drug questionnaire were current users of stomach medications, including antacids. Unless men with gastrectomy or peptic ulcer are protected against the development of large-bowel cancer, our data do not support the view that aluminium hydroxide can increase the risk for colorectal cancer. A. NOMURA Japan-Hawaii Cancer Study, G. N. STEMMERMANN Kuakini Medical Center, G. A. GLOBER Honolulu, Hawaii 96817, U.S.A.
National Institute for
Holly Hill, Hampstead,
Biological
Standards and Control,
A. J. GARRETT
London NW3 6RB
HAND-MIRROR CELLS IN T-CELL LYMPHOMA
SIR,-In your editorial
on
hand-mirror cells in leukaemia
(July 22, p. 195) you referred to an extensive cell-marker analysis of one case of acute lymphoblastic leukaemia by Stass et al.3 The blast cells were positive for acid phosphatase and terminal deoxynucleotidyl transferase (TdT) but T-cell-specific antigens were not investigated. We have seen a case with features very similar to that described by Stass et al. The blast SEROLOGICAL ANALYSIS OF BLAST CELLS
Microcytotoxicity test with absorbed rabbit serum as complement 4 tAbsorptions: 108 cells/ml of 1:4 diluted antiserum. $Rabbit anti-lymphocyte-serum absorbed with AB red cells, platelets, and several T lymphoid cell-lines. § Rabbit anti-A.L.L. made specific for human non-T non-B A.L.L. cells by absorptions with AB red cells, platelets, B-lymphoid cell lines, and thymocytes. Preparation and specificity of these antisera were described else*
HUMAN TUMOURS IN MICE AND RATS
SIR,-Your editorial (July 15, p. 138) and the letter from Dr Rostom and colleagues (Aug. 19, p. 428) rightly emphasise the values and some of the limitations of using xenografts of human tumours in immunodeficient animals as models for testing antitumour agents. Provided it is remembered that the greatest limitation of the system is that the tumour is a xenograft, the best model is one in which the implant is tumour tissue fresh from the patient. Passage of the tumours in vivo or in vitro often leads to alteration of certain characteristics, and in this laboratory, for example, a human melanoma in thymectomised, irradiated mice lost most of its capacity to produce melanin within 15 passages whilst still retaining a human karyotype and a rapid rate of growth. Rostom et al. seem to doubt your statement that xenografts rarely metastasise and claim that "few careful investigations of this have so far been made". They refer only to the work of 1.
Cruse, J. P., Lewin, M. R., Clark, C. G. Lancet, 1978, i, 1261.
where.s
cells had T-cell-specific antigens as well as p-glucoronidase, acid phosphatase, and TdT. The blast cells had no receptors for complemention, IgG or IgM, and no surface membrane Ig. They were recognised by several anti-human-T-cell antisera 1.
Ueyama, Y., Morita, K., Ochiai, C., Ohsawa, N., Hata, J., Tamaoki, N. Br. J. Cancer, 1978, 37, 644. 2. Franks, C. R., Boulger, L. R., Garrett, A. J., Bishop, D. Reeson, D., Perkins, F. T. Eur. J. Cancer, 1975, 11, 619. 3. Stass, S. A., Perlin, E., Jaffe, E. S.,Simon, D. R., Creegan, W. J., Robinson, J. J., Holloway, M. L., Schumacher, H. R., Am. J. Hemat. 1978, 4, 67. 4. Mittal, K. K., Mickey, M. R., Singal, D. P., Terasaki, P. I. Transplantation, 1968, 6, 913. 5. Boumsell, L., Bernard, A., Lepage, V., Lemerle, J., Dausset, J. Fed. Proc. 1978, 37, 1289.
