Genomic rearrangements in mouse C3H/10T1/2 cells transformed by X-rays, UV-C, and 3-methylcholanthrene, detected by a DNA fingerprint assay[superscript 1]

Genomic rearrangements occurring in C3H/10T1/2 cells transformed by X-rays were examined with a DNA fingerprint assay. Four multilocus and multiallele probes were employed (M, X, H10, and H16) that detect different families of minisatellite sequences dispersed throughout the genome. Genomic rearrangements were detectable only with probe M. This specificity may be explained by a genomic instability owing to a specific sequence or structure of DNA recognized by probe M. Genomic rearrangements were detected in 5 of 12 type III foci trans formed by 600 cGy of X-rays and in all clones isolated from a previously transformed clone exposed to a second dose of 600 cGy and recloned. The latter data suggest that the stage of transformation and the occurrence of genomic rearrangement induced by X-rays may be related. An intensity shift or a complete deletion of band 2 was common to these X-ray-induced clones, as well as to clones transformed by UV-C (1 of 5) or 3-methylcholanthrene (4 of 6). This band did not hybridize to probes for the retinoblastoma gene RB or for p53. We hypothesize that the loss of band 2 may reflect a significant genetic change in the transformation of 10T1/2 cells, perhaps representing the inactivation of a tumor suppressor gene other than RB or p53. Additional rearrangements occurred in X-ray-transformed clones; these rearrangements were not observed with the other carcinogens. Aside from the changes in band 2, however, no specific pattern of genomic rearrangement was associated with X-ray transformation, and the presence or absence of rearrangements did not correlate with tumorigenicity in syngeneic nonimmunosuppressed C3H mice

Enhancement of genomic instability by 17[beta]-estradiol in minisatellite sequences of X-ray-transformed mouse 10T1/2 cells

The female hormone 17[beta]-estradiol is involved in the development of breast cancer, an effect usually attributed to its capacity to stimulate the replication of preneoplastic and malignant cells. In this study, we report that 17[beta]-estradiol enhances the onset of genomic rearrangements, a type of genomic instability, in minisatellite sequences of malignant 10T1/2 mouse cells. Two malignant clones, X-ray-9 and F-17a, previously transformed in vitro by X-rays (600 cGys), and two non-transformed 10T1/2 mouse cell subclones (10T1/2b and 10T1/2c) were divided into two groups. The first group was incubated in the presence of 10[superscrip -5] M of 17[beta]-estradiol (dissolved in ethanol) for 5 days, while the second group was incubated for the same period in culture media containing 0.1% of ethanol. After the incubation both groups of cells were then subcloned, and their DNA was extracted and analyzed with the DNA fingerprinting assay using the probe M (core sequence: 5'-AGGC). A high frequency of genomic rearrangements was observed in the transformed subclones treated with 17[beta]-estradiol. Nine deletions or additions in minisatellite alleles were observed in six F-17a subclones, while 28 of those genomic rearrangements were found in the 12 X-ray-9 malignant subclones. On the other hand, for the non-transformed 10T1/2b and I0T1/2c cells, no genomic rearrangements were induced by the hormone. After the withdrawal of 17[beta]-estradiol from the transformed clone X-ray-9, no new genomic rearrangements were detected; while a second incubation with the hormone induced new deletions or additions in minisatellite alleles. This preferential enhancement of genomic instability in malignant 10T1/2 mouse cells suggests that 17[beta]-estradiol may accelerate the accumulation of mutations, and therefore may represent a mechanism by which the female hormone contributes to breast cancer development

Reconciling two opposing effects of radiation therapy : stimulation of cancer cell invasion and activation of anti-cancer immunity

Abstract : Purpose: The damage caused by radiation therapy to cancerous and normal cells inevitably leads to changes in the secretome profile of pro and anti-inflammatory mediators. The inflammatory response depends on the dose of radiation and its fractionation, while the inherent radiosensitivity of each patient dictates the intensity and types of adverse reactions. This review will present an overview of two apparently opposite reactions that may occur after radiation treatment: induction of an antitumor immune response and a protumoral response. Emphasis is placed on the molecu- lar and cellular mechanisms involved. Conclusions: By understanding how radiation changes the balance between anti- and protumoral effects, these forces can be manipulated to optimize radiation oncology treatments

Complexe anticorps monoclonal - phthalocyanines : évaluation comme outil de travail en photothérapie

La formation d'un complexe anticorps monoclonal - phthalocyanine est proposée en vue d'améliorer l'efficacité du traitement anti-tumoral appelé thérapie photodynamique. Cependant, on devait tout d'abord connaître le mode d'action de cette drogue. Nos études nous ont permis de vérifier qu'un A1C1-SPC moins polaire démontrait un plus grand niveau de photocytotoxicité. Ce fait fut relié au caractère amphibique des disulfonés A1C1-SPC où les deux groupements sulfonés se situaient sur des noyaux benzène adjacents. Cette propriété leur a permis de traverser efficacement la membrane cellulaire pour ensuite se diffuser uniformément dans le cytoplasme. Notre McAb a aussi démontré un fort potentiel avec sa constante d'association de 1.6x1010 M-1 et un nombre de sites d'attachement sur la cellule tumorale de 4.5x105. In vivo, la liaison sur la tumeur du McAb-I125 fut évidente alors que son niveau d'accumulation était directement proportionnel à la dose de McAb froid injectée. Notre système tumeur - McAb est valide qui et pourra être utilisé comme outil de travail pour étudier la photocytotoxicité d'un complexe McAb - phthalocyanine