European Journal of Cancer (1965)最新文献

BDF-1 mice implanted for various times and with different numbers of Ehrlich ascites cells were used as a model system to find out how early in the development of neoplasia the SCM-responding subpopulation of lymphocytes can detect cancer (SCM-test), as assessed by changes in intracellular fluorescein polarization in response to stimulation with phytohaemagglutinin and ascites cell extract (ACE). One hour after implantation of 7.5 × 10⁵ ascites cells SCM-responses to ACE were induced and PHA responses abrogated. At the threshold number of 3.5 × 10⁵ ascites cells per animal SCM-responses to both ACE and PHA were observed. Ascites cells killed by radiation did not induce changes in SCM-responses. Extrapolation of these data on the basis of body weight ratio indicates that a human tumour load of less than 10⁹ cancer cells might be detectable in the SCM-test.

A pyrazofurin-resistant subline of the Morris rat hepatoma 3924A has been isolated in vitro. These cells, designated subline 3924A/1P39-3, were 100-fold resistant to pyrazofurin, and showed cross-resistance towards 6-methylmercaptopurine riboside and 6-chloropurine riboside, but not towards 6-azauridine or arabinosyladenine. Measurement of cellular enzyme activities indicated that the level of adenosine kinase in the mutant was decreased to 2% of the value in the parental cell line, but activities of uridine kinase, adenosine deaminase, deoxyadenosine kinase and orotidine 5′-monophosphate decarboxylase showed no significant change. Despite the extensive deletion of adenosine kinase, the sensitivity of the mutant to adenosine toxicity was not greatly different from that of the parental 3924A cell line. Incubation of the cells for 20 hr in presence of 300 μM adenosine caused an increase of 43% in the adenine nucleotide pool of the 1P39-3 cells, as compared with an increase of 93% in the parental 3924A cells. In both lines 300 μM adenosine caused significant depletion in uridine nucleotides and phosphoribosylpyrophosphate pools. Nevertheless, uridine (1 mM) did not reverse the adenosine toxicity in either case. These cells have provided direct evidence that the antipyrimidine agent, pyrazofurin, is activated by adenosine kinase in rat hepatoma cells. The results also show that loss of adenosine kinase does not affect adenosine toxicity in these cells, suggesting that the toxicity may be attributable to free adenosine rather than overproduction of adenine nucleotides.

An aromatic analog of retinoic acid (Ro 10-9359), a synthetic compound known to arrest development and growth of chemically-induced skin papillomas and carcinomas of mice, exerts a marked inhibitory effect on induction and development of virus-induced papilloma (Shope) of rabbit skin. The intramuscular administration of 12.5, 50 and 200 mg/kg given twice weekly during the induction phase of the neoplasia substantially inhibited the growth of the papilloma, this inhibition being dose-dependent. When the animals bearing well-established tumors were given a relatively large dose (200 mg/kg) of the compound, there was remarkable inhibition of the papillomatous growths and complete regression occurred in about 60%. The transplantable carcinomas Vx2 and Vx7, both of which originated from the Shope virus-induced papilloma, were less sensitive than their original papillomas to this treatment.

Cell lines were obtained from nine individual spontaneous metastases of the murine mFS6 sarcoma by s.c. inoculation of lung deposits in syngeneic mice. When inoculated i.m., two lines (M4 and M7) from metastases had greater, and two (M8 and M9) had less metastasizing capacity than the primary mFS6 sarcoma. The remaining cell lines gave spontaneous metastases similar in incidence, number and weight to the primary mFS6 tumor. When inoculated i.v., M2 and M4 gave consistently more lung deposits than mFS6 cells, whereas cells from M1, M5, M6 and M8 produced fewer artificial metastases than the primary tumor. Eight individual lung metastases were disaggregated and tested for metastasizing capacity immediately after isolation from the lung parenchyma: spontaneous and artificial metastases from metastatic cells were similar to the primary tumor, except for one secondary which was less metastatic. The immunological characteristics of cell lines from metastases were studied by in vivo immunization and challenge. Seven lines from metastases and the primary tumor had weak cross-reacting transplantation antigens whereas two lines (M3 and M4) had no demonstrable antigenicity. Thus, cell lines from individual spontaneous metastases are heterogeneous in many respects, including metastasizing capacity. However in this model metastasis does not appear to be the expression of strong selection of variant cells with increased metastatic potential.

Oestradiol-17β was determined in human breast tumours by radioimmunoassay and gas chromatography-mass spectrometry. Simultaneous determination of the oestradiol and progesterone receptor content was carried out. Oestradiol receptor positive tumours contained a greater statistically significant oestradiol concentration than receptor negative tumours.

Our results indicate that (a) the use of gas chromatography-mass spectrometry is more valid in measuring endogenous oestradiol-17β content, (b) false negative receptor assays due to the presence of endogenous oestrogens are unlikely.

We have in the past proposed the hypothesis that virus-associated lymphoma development in AKR mice might be in some way related to the occurrence of antibody activity to murine leukemia virus (MuLV). Here we have attempted to test this hypothesis using the ¹²⁵I-protein A radioimmunoassay recently developed in this laboratory. Previous findings in naturally derived (AKR × CBA/H-T6Crc) F₁ confirmed the presence of MuLV, moreover, at levels comparable to or indeed occasionally in excess of, the AKR. Despite this, tumours were uncommon during the first year of life and no antibody activity could be detected at this time. It was later noted that lymphomas did occur in the F₁ but in the second year. To test our hypothesis that there may be a possible association between tumour resistance and antibody activity, these hybrids have been investigated further during this later period.

In addition, we have examined other groups of mice in which we have attempted to prematurely induce antibody activity experimentally.

In both these situations there was no apparent relationship between tumour development and the presence of anti-MuLV activity.

Nude mice of BALB/c background were utilized for the heterotransplantation of tissues derived from 4 forms of natural bovine lymphosarcoma. The growing tumors have been established from adult case tumor (6 out of 22 attempts), from calf case tumor (2 out of 5 attempts), from skin case tumor (18 out of 30 attempts) and from thymic case tumor (3 out of 11 attempts). In all, successful tumor growth was observed in 29 out of 68 transplanted natural bovine lymphosarcoma cells. Transplanted tumors from skin case grew fast, metastasized and then became lethal to the host. However, transplanted adult case tumors regressed and no spread of tumor cells was observed.