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Carcinogenic Chemicals – Carcinogenesis

by Carlo Raj, MD
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    00:01 This flow chart. Do not let it intimidate you. Do not let it overwhelm you. That is not the point.

    00:07 The point of this is, I am going to show you, step by step how you are going to take every one of this boxes and apply it to what you need to know for carcinogenesis.

    00:21 Once we have discussed the entire flow chart, you will come back and take a look at it and my goodness you will tell yourself this is really simple. It is.

    00:32 Everything that you need to know about carcinogenesis is in this flow chart.

    00:35 I will take each one of this boxes and I will spend prudent time so that you are able to effectively learn, what then caused mutation to the normal cell. Take a look at the top of this flow chart.

    00:49 You have the normal cell. And the normal cell got exposed to whatever type of carcinogen.

    00:54 And as the mutation continues eventually, take a look now. You are going to move from the normal cell, and as you go through every box or we shall be going through every box. At some point in time, you have so much malignancy with increased nuclear to cytoplasmic ratio, that there is every possibility that the cancer may then rupture through the membrane and result in? Take a look at the bottom portion of this flow chart and over to your right you will notice that now the malignant cell has ruptured through the membrane resulting in metastasis.

    01:27 Our job and objective is to make sure that we go through the entire flowchart from top to bottom.

    01:32 Take in the boxes that we see in the side and I will show you how to utilize, how a chemical mutation genetically, what have you, may result in a cancer.

    01:44 Our first order of business will be the box on your left. I will walk you through chemicals that are responsible for developing cancer. Radiation and viruses. And once we are done, I will keep coming back to this flowchart in which you will see exactly as to where you are located.

    01:59 Let's begin. The chemicals. Where we are on that flowchart, over to your left is that box.

    02:07 Important chemicals that you would want to know for your boards responsible for developing cancer.

    02:12 Now before we begin, there is something called a Ames test. It screens for carcinogens.

    02:18 It detects mutagenic effects on bacterial cell in culture. Assumes that mutagenicity in vitro, in the lab correlates with the carcinogenicity in-vivo, your body. This is called a Ames test.

    02:33 If i were you, I would know at least the definition of Ames test. Screening for carcinogens.

    02:40 Our first chemical is one in which let's say that you smoke your meat.

    02:44 An entire population that does this quite commonly would be out in the far east.

    02:48 You are thinking about Japan and perhaps China. To the point where the government itself has got involved and wishes to educate it's society so that it tells them to not smoke their meat and so therefore not consume nitrosamine is my topic. And the reason for that is, consumption of nitrosamine, via smoking your meat then results in developing a type of gastric adenocarcinoma.

    03:13 In the United States, it's incidence is dropping becaause, well, we don't smoke our meats as much and we have done a good job in terms of educating our society with consumption of nitrosamines.

    03:25 First chemical here that we are looking at that may result in a type of cancer. Know it well.

    03:32 Asbestos. With asbestos, this is a topic that we cover in pulmonology especially when we start talking about asbestos in development of lung cancer.

    03:43 That's your first order of business. Now with asbestos, who is your patient? Well all that stuff we will talk about later. With asbestos, it will come specifically under Restrictive Lung Disease in Pulmonology.

    03:56 Restrictive Lung Disease. And under restrictive lung disease, we will talk about a topic called pneumoconiosis.

    04:01 Are you with me? And if you are confused, that's okay because in pulmonology we will be spending quite a bit of time with pneumoconiosis.

    04:10 Asbestos. Your patient might have been working in a naval shipyard. Or maybe your patient was a roofer.

    04:19 And with exposure to asbestos, with different types of fibres that the patient is breathing in.

    04:27 One is called chrysotile, and by chrysotile it means that it's a serpentine or the curved like fiber, which is quite common. Not as carcinogenic as the other type of fibre and it's known as your, well, it's dangerous. It's straight and brittle. And that type of asbestos fiber when breathed in or inhaled, may then result in a bronchogenic carcinoma. The only cause in United States of mesothelioma is asbestos.

    04:57 Now, those patients that are watching commercials, and on your commercials there is mesothelioma, always comes on.

    05:09 And therefore patient would think the most common type of lung cancer that asbestos causes is mesothelioma.

    05:16 That could not be further from the truth. The most common type of lung cancer that one would develop after exposure to asbestos especially the amphibole particle. The amphibole would be the straight and brittle.

    05:29 This is much more carcinogenic. Would be bronchogenic carcinoma. We'll talk about this later but this is a chemical.

    05:36 Also perhaps renal cell carcinoma but the big one that you are paying attention to will be lung.

    05:42 Nitrosamines, asbestos. Other chemicals that you need to know that may result in cancer include chromium and nickel. What might you be doing here, in which the patient develops lung cancer? Mining.

    05:55 Okay? Mining. Arsenic? mining as well. Now, when you say mining, be careful, because you might be mining for coal and that is completely different. Here you're mining for, well, different metals.

    06:09 And when you are mining you might then be exposed to different chemicals. So, maybe it's chromium and nickel, maybe it's arsenic. Now, when you hear arsenic, by reflex you should be thinking about apart from the skin, you should also be thinking about the liver. Two major organs here. Arsenic, upon exposure, squamous cell cancer of the lung, squamous cell cancer of the skin. And in the liver, a condition known as angiosarcoma of the liver. Angiosarcoma could take place in a number of organs but most likely you should be thinking about the liver. Chromium and nickel, arsenic. Topic, chemicals that give rise to cancer. Other chemicals that you must know that are responsible for developing cancer, vinyl chloride. What industry is your patient working in and what is your patient being exposed to, to develop angiosarcoma of the liver with vinyl chloride. Plastic. Vinyl chloride, a chemical that might be, or is considered to be carcinogenic. Now this one is interesting. It's unfortunate. Your patient comes in with a cancer, and indications show that chemotherapy must be started. And the particular chemotherapeutic agent that you choose to administer your patient will be an alkylating agent. Unfortunately while treating your patient for cancer with alkylating agent, your patient develops a secondary cancer. Unfortunate. It might be either leukaemia or lymphoma.

    07:44 That is how to interpret alkylating agent. Napthylamine. Napthylamine could be found with perhaps cigarette.

    07:54 And with cigarettes though there is other chemicals including aromatic amines, hydrocarbons are big ones.

    08:01 And when you are smoking, the type of cancers that you may develop include in the lung, small cell lung cancer and squamous cell lung cancer. Both of those. Lung, also urinary bladder.

    08:14 So with smoking you might then develop transitional cell cancer of the urinary bladder. We'll talk further about that later.


    About the Lecture

    The lecture Carcinogenic Chemicals – Carcinogenesis by Carlo Raj, MD is from the course Cellular Pathology: Basic Principles.


    Included Quiz Questions

    1. Links carcinogenesis in human populations with mutagenicity caused in bacterial cultures
    2. Detects mutagenic effects on viral cells in culture
    3. Correlates mutagenicity in vivo to carcinogenicity in vitro
    4. Screens for mutated cells
    5. Identifies bacterial carcinogens
    1. Gastric adenocarcinoma
    2. Colorectal cancer
    3. Lung carcinoma
    4. Renal cell carcinoma
    5. Hepatic sarcoma
    1. Nasopharyngeal carcinoma
    2. Renal cell carcinoma
    3. Mesothelioma
    4. Lung carcinoma
    5. Bronchogenic carcinoma
    1. Nitrosamines
    2. Asbestos
    3. Chromium
    4. Arsenic
    5. Nickel
    1. Napthylamine
    2. Vinyl chloride
    3. Arsenic
    4. Chromium
    5. Alkylating agents

    Author of lecture Carcinogenic Chemicals – Carcinogenesis

     Carlo Raj, MD

    Carlo Raj, MD


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