Enhancement by cytotoxic agents of artificial pulmonary metastasis

Steel, G. Gordon; Adams, K

doi:10.1038/bjc.1977.247

Cited by 36 publications

(13 citation statements)

References 10 publications

(15 reference statements)

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“…It may therefore be that the condition of the lung which makes it more susceptible to Cy lung damage also makes it more susceptible to tumour implantation. Strain differences make such conclusions speculative at present, since in C57 mice the optinmal time for Cy enhancement of lung colonies is 2-4 days (Steel & Adams, 1977). However, these particular mice may have delayed development of lung changes, since their median survivals following lung irradiation were between 200 and 310 days, whereas in CBA mice the medians ranged from 95 to 130 days, which are similar to the median survivals reported by other investigators (Steel et al, 1979).…”

Section: Discussionsupporting

confidence: 77%

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Cyclophosphamide-induced lung damage in mice: protection by a small preliminary dose

Collis¹,

Wilson²,

Jones³

1980

Br J Cancer

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Summary.-Cyclophosphamide (Cy) produces an interstitial pneumonitis in CBA mice. The extent of the lung damage has been quantified by measuring the increase in ventilation rate over 6 weeks after an i.p. injection of Cy 200,250 and 300 mg/kg. A dose-dependent response was found. When a preliminary ("priming") dose of Cy at 50 mg/kg was given 7, 9 or 14 days before a single large dose of 250 mg/kg, lung damage was reduced, as shown by a smaller increase in ventilation rate than in those receiving 250 mg/kg alone, and this difference was significant (P < 0 01) in the Day-14-and highly significant (P<0-001) in the Day-7-"primed" groups. When primed less than 7 days before, there was a relative increase in ventilation rate, which was statistically significant (P <0.01) in the Day-i -primed group. Similar effects were also seen in the survival of the mice.

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Section: Discussionsupporting

confidence: 77%

“…injections of tumour cells (van Putten et. al., 1975;Carmel & Brown, 1977;Steel & Adams, 1977). In the C3H mice, enhancement was optimal when the drug was given 24 h before the tumour cells (Carmel & Brown, 1977).…”

Section: Discussionmentioning

confidence: 99%

Cyclophosphamide-induced lung damage in mice: protection by a small preliminary dose

Collis¹,

Wilson²,

Jones³

1980

Br J Cancer

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“…When counting colonies, care was also taken to distinguish between tumour and host-derived colonies . Lung-colony assay The lung colony assay has been described in detail for the LL tumour by Steel & Adams (1977). In this study all implants consisted of viable cells plus 106 heavily irradiated feeder cells and 106 15 gum diameter plastic microspheres.…”

Section: Methodsmentioning

confidence: 99%

Identification of a subpopulation of MeCCNU resistant cells in previously untreated Lewis lung tumours

Stephens¹,

Adams²,

Peacock³

1984

Br J Cancer

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“…Various authors (Van Putten et al, 1975;Steel & Adams, 1977) showed that cyclophosphamide pre-treatment could increase, by more than 1000-lold, the number of lung colonics in a mouse mammary tumour model. This effect was related to drug cytotoxicity against host tissue .…”

Section: Discussionmentioning

confidence: 99%

In vivo emergence of a highly metastatic tumour cell line from a rat rhabdomyosarcoma after treatment with an alkylating agent

Antoine

Pauwels²,

Verrelle³

et al. 1988

Br J Cancer

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Summary Rats bearing a transplanted nickel-induced rhabdomyosarcoma (RMS 9-4/0), treated with chlorozotocin (CZT), an alkylating agent, showed an amplified metastatic invasion of the lung (median of 165 lung tumour nodules, compared to 3 for untreated controls). A higher level of metastatic invasion (200 nodules) was reached spontaneously after the grafting of the S4T line, which was obtained by successive in vivo passages of RMS 9-4/0 cells in CZT treated rats. S4T tumour cells also invaded the liver and a considerable proportion of the lymph nodes. The NT4T line, obtained by successive in vivo passages in untreated rats, showed a lesser degree of enhancement of metastatic capacity (57 nodules). Both derived lines proved to be more aggressive than the parental, proliferated more rapidly, and were resistant to CZT toxicity. Only the non-treated lineage became more resistant to NK lysis. The S4T line lost its myogenic differentiation and was best described as a fibrohistiosarcoma, whereas NT4T did not. Chromosome analysis demonstrated a reduced range of chromosome number per cell in both lines. We conclude that both S4T and NT4T tumours became more metastatic than RMS 9-4/0 as the result of tumour progression through in vivo passages, and that in addition S4T acquired a spontaneously higher metastatic potential, similar to that which occurred in rats grafted with RMS 9-4/0 or NT4T tumours and treated by CZT. This suggests an inheritable mutation in the S4T line.A major problem of cancer therapy is the emergence of tumour subpopulations resistant to the treatment. The probability that a tumour will generate resistant variants could be related to genetic instability (Goldie & Coldman, 1984;Stephens et al., 1986 Davies, 1982). Repair mechanisms may allow mutated cells to survive, and increase both tumour drug resistance and phenotypic heterogeneity.We have described the enhancing effect of a nitrosourea, chlorozotocin 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-glucopyranose (CZT), on the metastatic ability of RMS 9-4/0, a rat rhabdomyosarcoma (Poupon et al., 1984). We hypothesized that this action was due to the emergence of a subpopulation of the RMS 9-4/0 tumour, that was both resistant to CZT and highly metastatic. We failed to obtain a selection for CZT resistance in the primary tumour because the treated rats were rapidly killed by the growth of lung metastases. To overcome this, the treated primary tumour cells were injected into new recipients that were also treated and this cycle was repeated until a fully resistant population was obtained. The metastatic ability of these cells was then studied. A group of the tumour-bearing rats were not drug-treated and gave rise to the NT(x)T tumour lineage, where (x) designates the number of cycles performed. When rats were moribund the tumour was excised, finely minced with a scalpel, and then allowed to grow in the complete medium described above. At confluence, cells were injected s.c. into new animals. Part of the cells were frozen for further analyses. Materials and me...

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Enhancement by cytotoxic agents of artificial pulmonary metastasis

Cited by 36 publications

References 10 publications

Cyclophosphamide-induced lung damage in mice: protection by a small preliminary dose

Cyclophosphamide-induced lung damage in mice: protection by a small preliminary dose

Identification of a subpopulation of MeCCNU resistant cells in previously untreated Lewis lung tumours

In vivo emergence of a highly metastatic tumour cell line from a rat rhabdomyosarcoma after treatment with an alkylating agent

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