Probable cause of Death in animal carcinogenicity modal

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Kvachhani
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Probable cause of Death in animal carcinogenicity modal

Can any one suggest the probable cause of death in case of animal cancer model (mostly mice) or in regulatory carcinogenicity study? suppress immunity leading to secondry infection is could be the main cause? or intoxication of the tumer tissue & its secretion? or any other?

Omai
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One possibility is the animal

One possibility is the animal could show organ failure due to overabundance of mets produced from the primary tumor.
I don't usually see secondary infection if the animals are housed in a clean facility.

Can you please clarify your question? Do you have a specific model you are looking at?

Kvachhani
Kvachhani's picture
Thanks for reply

Thanks for reply

Yes organ failure might be a possibility,

I am talking any animal model for cancer, as i shown mortality in both for animal model and in carcinogenicity study in mice or rat for safety accessment of the drug.

My question is, their is heavy mortality in animal if we introduce any cancer in animal or if we conduct carcinogenicity study in mice or rat, what is the main cause for the mortality when tumer is developed?

i shows animal are very emaciated when they dies, malnutrition due to draining and utilization of nutriant by developing tumer is the cause?

Omai
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Here are a couple of links

Here are a couple of links that I think you will find very informative.

A discussion on this very topic
http://www.protocol-online.org/biology-forums/posts/20426.html

A paper devoted to this topic
http://protein.bio.msu.ru/biokhimiya/contents/v70/full/70091277.html

This paper is fascinating. I never quite thought about cancer in this particular way. I really suggest giving it a read. Here is a quote from the article on the topic of killer cancer:

"The killer function of cancer cell is its specific feature, which is not settled with its other properties, such as unregulated proliferation or metastasizing. Indeed, the active proliferation of cancer cells seems unlikely to be as disastrous as it is, because every day in the organism of an adult human dozens of billions of cells are dividing compensating the loss of dead cells, and this is manifold higher than the proliferative pool of the largest tumor. And even metastases, which are foci of ectopic growth of relatively small numbers of cells, do not explain the death of the organism (except the above-mentioned rare situations when just the tumor location is fatal). In most cases, not local but general manifestations of tumor growth play the leading role in the clinical picture of cancer.

The killer function of a cancer cell is a universal property: in the absence of treatment the lethal outcome is inevitable, independently of the tumor type and location, its ability to relapse and metastasize, induce cachexia, and affect biochemical parameters. And finally, this function is specific for cancer cell, because normal cell physiology presents no examples of similar activity (nearly all other inherent features of the cancer cell are found in normal cells during some developmental stages, in particular, in stem cells [39]). Green and Evan in their “paradoxical hypothesis” [40] supposed that the platform necessary and sufficient for carcinogenesis could be provided only by two main processes, deregulation of proliferation and suppression of apoptosis. Other properties of tumor (invasion, stimulation of angiogenesis, escaping the immune response, etc.) are secondary and inherent to any tissue during its expansion. Assuming similarity of many features of tumor and normal growing tissue, it should be noted that neither the growing nor resting normal tissue displays the killer ability."

These links mention many causes of death due to cancer including organ failure due to tumors disrupting normal organ function, depletion of nutrients and blood vessels from an organ to the invading tumor, homeostasis imbalance due to abnormal hormone production by a tumor, overworking of the immune system for weeks to months while it fights the tumor leading to energy exhaustion and death, autoimmune disease . . .

A little off topic, here is another very interesting quote from the article:
"Mutagenesis is closely linked with vital activities and, therefore, is omnipresent: in every cell of the organism thousands of acts of the genome injury occur because of errors in replication and repair, spontaneous depurinization, deamination of methylcytosine, influence of reactive oxygen species, shortening of telomeres [9, 11, 48-54]. And mutagenic effect of apoptosis also should be added during which phagocytizing cells uptake the genetic material of dying cells. Considering, first, the involvement of all cells of the organism in this process, second, scale of this natural transfection (every day ~1011 cells dies in the body of an adult human and ~0.6 g DNA is liberated), and, third, continuity of this transfection during the whole life, its essential contribution, although yet unestimated quantitatively, to general mutagenesis is very likely. In any case, a possibility was shown of such a “horizontal” transmission of genetic information and tumor transformation as a consequence [55, 56]. As DNA repair mechanisms are imperfect, the mutation rate varies in the limits of 10-4-10-8 mutation/gene per cell division [9, 11, 57], increases with age, and affects all tissues [11, 50, 58-61]."

I never considered transformative DNA being picked up through phagocytosis and conferring a tumor phenotype through transfection.

Wow.

Any and all comments are welcomed.

Omai

Kvachhani
Kvachhani's picture
Thanks i got lots of

Thanks i got lots of information from your reply.

my concept is almost cleared.

Thanks