Mutagens and carcinogens | Biomolecules | MCAT | Khan Academy — Transcript

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1. 0:01Voiceover: So, today we're going to talk about
2. 0:02mutagens and carcinogens
3. 0:04and how they can cause DNA damage,
4. 0:07but first I want to review the central dogma
5. 0:09of molecular biology and how the genetic information
6. 0:12of a cell is stored in the form of DNA,
7. 0:15which is then transcribed to form RNA
8. 0:17and then translated to generate protein.
9. 0:20Now, nucleotides from DNA are transcribed
10. 0:23to their complementary forms on RNA,
11. 0:25which are then read as codons, or groups of three,
12. 0:28to code for specific amino acids in a larger protein.
13. 0:31Now, if you mutate one of the nucleotides on DNA,
14. 0:34like turn this thymine base into an adenine base,
15. 0:37then that will affect the RNA sequence
16. 0:39and ultimately the protein that follows.
17. 0:41So, we say that mutations are mistakes in a cell's DNA
18. 0:45that ultimately lead to abnormal protein production.
19. 0:48So, what is a mutagen?
20. 0:51Well, a mutagen is any chemical substance
21. 0:54or physical event that can cause genetic mutations.
22. 0:58Chemical substances, like certain poisons,
23. 1:00could be mutagens or physical events, like UV light
24. 1:03or different kinds of radiation could also be mutagenic,
25. 1:07and we classify mutagens into two different categories.
26. 1:10So, let's say we have a person over here.
27. 1:12A mutagen could be classified as endogenous,
28. 1:15if it comes from inside this person's body,
29. 1:17and it's some mutagen that's already found in the organism,
30. 1:21but an exogenous mutation is one that comes from
31. 1:23outside the affected organism,
32. 1:26something that's from the external environment.
33. 1:29So, what are some examples of some endogenous mutagens?
34. 1:32Well, the most significant endogenous mutagens
35. 1:35are what we call reactive oxygen species or ROS,
36. 1:39and ROS are naturally occurring metabolites
37. 1:42in the human body that are produced by
38. 1:44mitochondria during oxidative phosphorylation.
39. 1:47So, if we have this guy here,
40. 1:49who's about to chow down on a big meal,
41. 1:50you can expect that during the metabolism of the meal,
42. 1:53his mitochondria will produce a bunch of ROS,
43. 1:56like O2 dot minus, which we call superoxide,
44. 1:59which is an oxygen molecule with one extra electron,
45. 2:03as well as some hydrogen peroxide,
46. 2:05which is another ROS that your body can produce.
47. 2:08Now, reactive oxygen species, as you may be able to tell
48. 2:11by their name, contain oxygen, like both of these
49. 2:13examples do, but they're also highly reactive with
50. 2:16different cell components, including DNA,
51. 2:19and by reacting with DNA, they can actually cause
52. 2:21significant damage to a cell's genetic code.
53. 2:24One example of this type of damage is
54. 2:26the double-strand break, and ROS can actually break
55. 2:30a DNA's double helix into two smaller pieces,
56. 2:33and you can see why this type of a reaction
57. 2:35could cause a mutation, since it quite significantly
58. 2:38changes the structure of the cell's DNA.
59. 2:40The next type of DNA damage that ROS can cause is
60. 2:43base modification, and that's when
61. 2:46the nucleic acid bases are changed or swapped around,
62. 2:49and that can pretty readily cause point mutations
63. 2:52or maybe even other kinds.
64. 2:54Now, you may be wondering why would a cell
65. 2:55ever make something that could damage itself?
66. 2:57Well, it turns out that ROS actually have
67. 2:59a couple of beneficial effects on a cell,
68. 3:02and cells actually have a couple of ways
69. 3:03to make sure that they don't cause damage,
70. 3:05but sometimes ROS levels get really high,
71. 3:07and cells can't deal with them anymore,
72. 3:10and we call this oxidative stress, and antioxidants
73. 3:14are something that your doctor might have told you
74. 3:15that are good for you, and it turns out that part of what
75. 3:18antioxidants do is help make sure that ROS
76. 3:20don't damage your DNA.
77. 3:22Now, let's look at a couple examples of
78. 3:24exogenous mutagens, and there are
79. 3:26many different types of exogenous mutagens,
80. 3:28but we're really only going to talk about two.
81. 3:30Now, intercalators are one example,
82. 3:33and one of them is called ethidium bromide,
83. 3:36which you may be familiar with if you've ever done
84. 3:37a PCR experiment before, and what ethidium bromide
85. 3:41will do is it will jump into a DNA double helix
86. 3:44and stick itself between the two strands,
87. 3:47and when these intercalators intercalate into DNA,
88. 3:50they can deform the structure of the DNA
89. 3:53and cause some serious problems.
90. 3:55Base analogs, like 5-bromouracil,
91. 3:58which we also call 5-BU, pretend to be a certain base,
92. 4:02but then act differently than that base normally would.
93. 4:05So, in the case of 5-BU, it's an analog of uracil
94. 4:08and looks a lot like it, but once it's incorporated
95. 4:10into DNA, it can shift between two different forms.
96. 4:14In its keto-form, it will pair best with adenine.
97. 4:17While it's in enol-form, it will pair best with guanine.
98. 4:20Now, if you're familiar with organic chemistry,
99. 4:23you might know that 5-BU can convert between
100. 4:25its keto and enol form through something called
101. 4:28a tautomerization reaction, and overall you can see how
102. 4:31this base analog might be able to
103. 4:33induce mutations in a DNA strand.
104. 4:37Now, the last thing we're going to talk about is
105. 4:38what a carcinogen is.
106. 4:40Now, carcinogens can be mutagens,
107. 4:42but not all of them are, but in general,
108. 4:44you can say that a carcinogen is something
109. 4:46that can lead to cancer, which, if you remember,
110. 4:49is when cells in an organism divide uncontrollably
111. 4:51and can form big masses of cells, called tumors.
112. 4:54Now, some carcinogens will work by making mutations
113. 4:57in DNA that lead to cancer, but sometimes they might
114. 5:00carry out their effects simply by increasing the rate
115. 5:02at which a bunch of cells divide,
116. 5:04without actually affecting their DNA,
117. 5:06and some examples of carcinogens are
118. 5:08tobacco, which come from cigarettes,
119. 5:10asbestos, which used to be used as home insulation,
120. 5:13and even UV radiation.
121. 5:16So, what did we learn?
122. 5:18Well, first we learned that mutagens are
123. 5:20chemical or physical substances or events
124. 5:23that can increase the probability of
125. 5:25genetic mutations occurring.
126. 5:28And next we learned that carcinogens are things
127. 5:30that lead to cancer, and while they can be
128. 5:32mutagenic as well, they aren't necessarily mutagenic.