Differential effects of nitrogen mustard in vivo on the cancer and host cells in MCa-11 tumours.
We analysed the effects of nitrogen mustard (HN2) on the growth, cell cycle distributions, and ratios of tumour cells to host cells for MCa-11 tumours grown in vivo. Treatment of tumour-bearing BALB/c mice with 3 mg/kg of HN2 produced a significant slowing of MCa-11 tumour growth. Seventy-two hours after treatment in vivo with either 3 or 4 mg/kg of HN2, the host cells in the treated tumours showed a significantly decreased G0/G1 peak and an increased G2/M peak (P < 0.01), whereas the cancer cells in the treated tumours showed significant increases in the G0/G1 peak coupled with relatively decreased proportions of S and G2/M tumour cells (P < 0.001). The ratio of the total number of cancer cells to the total number of host cells in the tumours was significantly increased 72 h after HN2 administration (P < 0.01). Thirty-two days after treatment with HN2, the cell cycle distributions of the host and tumour cells in the treatment and control tumours had returned to being identical, but the ratio of the total number of cancer cells to the total number of host cells remained increased in the treated tumours (P < 0.01). These results show that the administration in vivo of HN2 can lead to entirely different cell cycle effects for the host and cancer cells in the same tumour, and that the partial growth arrest of MCa-11 tumours from HN2 treatment may be due in part to the preferential destruction of host cells rather than solely to a direct cytotoxic effect on the cancer cells.
Bose
K K
KK
Department of Surgery, Medical College of Ohio, Toledo 43699-0008, USA.
Zahurak
M L
ML
Allison
D C
DC
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D004396:Coloring Agents; D004247:DNA / Q000032:analysis; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D008466:Mechlorethamine / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012394:Rosaniline Dyes; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D016588:Anticarcinogenic Agents; D004396:Coloring Agents; C007722:Feulgen stain; D012394:Rosaniline Dyes; D008466:Mechlorethamine; D004247:DNA