Teratogens

Question 1

Teratogen

Answer 1

an extraneous agent that induces a structural defect and/or functional alteration in an organism during prenatal development

Question 2

What is the effect of a teratogen?

Answer 2

Teratogens disrupt specific developmental processes (eg. inducing apoptosis or blocking signaling pathways, etc)

Question 3

Effect of teratogens on birth defects

Answer 3

The risk that a teratogen will cause a birth defect in any given embryo is not 100%. At the same dose and timing, some embryos will be affected by a teratogen, while others continue to develop normally. The outcome depends on the genetic makeup of both the mother and the embryo and is influenced by other environmental factors (teratogens themselves falling under the category of an “environmental factor.”)

Question 4

Examples of environmental factors that influence the outcome on the genetic makeup of both the mother and the embryo

Answer 4

• Increasing maternal use of prescription drugs during pregnancy.
• Increasing rates of pre-pregnancy obesity.
• The development of assisted reproductive technologies.
• The frequent introduction of new compounds in manufactured goods.

Question 5

Dose-Response Relationship

Comparison of mutagens and teratogens

Answer 5

Teratogens have a clear dose-response relationship. In general, the higher the dose, the more severe the resulting birth defect will be, as more and more cells in the embryo are damaged or destroyed. There is no dose-response relationship with mutagens. Once the critical genetic mutation(s) have occurred, the cancer cell begins to grow and follows a predictable path. For the most part, it doesn’t seem to matter how many other “passenger” mutations are present in the cancer cell.

Question 6

Threshold dose
(Comparison of mutagens and teratogens)

Answer 6

Most teratogens have a dose below which all embryos are unaffected. There is no similar completely safe dose of mutagens. A degree of risk that a critical cancer gene could be randomly mutated exists at any dose of mutagen.

Question 7

Critical period

Comparison of mutagens and teratogens

Answer 7

There is a critical period during development during which a teratogen causes its associated birth defects. The teratogen has to be present when the target organ is developing to be able to disrupt its formation. In contrast, mutagens can act at any time during a person’s life to cause cancer causing mutations.

Question 8

Dose-incident relationship

Comparison of mutagens and teratogens

Answer 8

For both teratogens and mutagens, the fraction of people who develop disease increases with increasing dose. The higher dose of mutagen, the more likely a critical cancer gene will be randomly mutated and cancer will begin. The higher the dose of teratogen, the more likely an embryo will be above its individual maximum tolerance level and develop a birth defect.

Question 9

How do you determine whether something is a human teratogen?

Answer 9

1. There is an abrupt increase in the frequency of a particular defect or group of defects (syndrome).
2. The increase of defects is associated with the use of a new drug or the widespread exposure to a chemical or environmental change.
3. The agent was present during the critical stage of development.
4. The agent produces a particular pattern of birth defects in animal studies. 5. The agent crosses the placenta and there is a dose-response relationship. 6. The mechanism of teratogenesis makes biological sense.

Question 10

Radiation as a Teratogen

Answer 10

Ionizing radiation can cause physical damage to the brains of developing fetuses at an 0.05-0.5 Gy acute dose, during the period of 8-15 weeks post-conception.

Question 11

Radiation as a Mutagen

Answer 11

Ionizing radiation causes DNA mutations. X-rays cause large chromosomal abnormalities and smaller changes as well. One type of non-ionizing radiation, UV light, can cause missense and nonsense mutations.

Question 12

Radiation as a Carcinogen

Answer 12

Any time random mutations are occurring, the risk for cancer increases above baseline. Melanoma is strongly linked to UV light exposure, which only penetrates the top layer of the skin.

Question 13

Radiation as a Carcinogen

Answer 13

Any time random mutations are occurring, the risk for cancer increases above baseline. Melanoma is strongly linked to UV light exposure, which only penetrates the top layer of the skin.

Question 14

Mutagen

Answer 14

An agent that causes changes to the sequence of an individual’s DNA. Mutagens can also cause less drastic changes: single base pair substitutions and small insertions and deletions.
Viral elements that insert themselves into a host genome are mutagens.

Question 15

Clastogen

Answer 15

A mutagen that can cause large chrosomsomal breakages and rearrangements, such as translocations, deletions, and inversions

Question 16

Aneuploidogen

Answer 16

A mutagen that can cause aneuploidy

Question 17

Somatic mutation

Answer 17

Occurs in a non-germ cell

Question 18

Germline mutation

Answer 18

Occurs in a germ cell (sperm or egg). Only germline mutations can be passed on to the next generation

Question 19

Carcinogen

Answer 19

An agent that promotes carcinogenesis, the formation of cancer

Question 20

How do carcinogens promote cancer?

Answer 20

One way this can happen is by DNA mutagenization.
Almost all mutagens are also carcinogens. Mutagenic events happen at random positions within the genome, when the mutagen physically interacts with the DNA at that site, altering its structure. By random chance, mutagens will sometimes hit genes that regulate cell survival and proliferation. Somatic mutations in these key oncogenes and tumor suppressors cause cancer to develop in that cell.

Question 21

How can carcinogens act by not mutagenizing the DNA?

Answer 21

Carcinogenic agents could also interfere with the immune system, signaling, or cell behavior in a way that accelerates cancer growth.

Question 22

What are the 3 major classes of carcinogenic agents.

Answer 22

Radiation, chemicals, and viruses

Question 23

Radiation

Answer 23

Radiation is fast moving energy emitted as particles or waves. It’s a teratogen, mutagen, and carcinogen.
- two categories: non-ionizing and ionizing.

Question 24

Non-ionizing radiation

Answer 24

low frequency radiation that disperses energy through heat and increased molecular movement. It includes visible light, ultraviolet light, microwaves, ultrasounds, MRIs, etc.

Question 25

Ionizing radiation

Answer 25

• Dangerous high frequency radiation that includes alpha and beta particles, gamma rays, and X-rays.
• can directly damage proteins, DNA, and other molecules in cells by transferring so much energy that it frees electrons from atoms.
• Can also generate free radical species that then go on to damage other molecules.

Question 26

When there is a significant and sudden rise in a particular type of birth defect in a particular place or group of people, it takes detective work to identify the teratogen that is responsible.
What are the criteria that need to be met for something to be a NOVEL TERATOGEN:

Answer 26

1) The agent must be present during the critical stage of development.
2) The agent produces a particular pattern of birth defects in animal studies.
3) The agent crosses the placenta and there is a dose-response relationship.
4) There is an abrupt increase in the frequency of a particular defect or group of defects (syndrome). 5) The increase of defects is associated with the use of a new drug or the widespread exposure to a chemical or environmental change.
6) There is an absence of other factors to explain the observations.
7) The mechanism of teratogenesis makes biological sense.

Question 27

What would happen if CRBN is knocked out?

Answer 27

Limb defects

Question 28

What is microcephaly?

Answer 28

Congenial condition associated with incomplete brain development, abnormally small head

Question 29

How was it concluded that the

Answer 29

The first evidence supporting the role of ZIKV in microcephaly was the analysis of two pregnant women in Paraíba, Brazil, whose babies had been diagnosed with microcephaly while still in the womb. The results revealed the presence of the ZIKV in samples of their amniotic fluid. Shortly thereafter, the virus was also found in the brains of miscarried fetuses with microcephaly. ZIKV was then found to infect and kill neuronal progenitor cells in model systems.

Question 30

What are the modes of transmission and process of replication of ZIKV?

Answer 30

zoonosis. ZIKV is spread between people by the Aedes aegypti mosquito, which lives throughout the world in tropical areas. When a mosquito bites someone, it injects some fluids into the skin to numb the area. The virus is passed into the person within these fluids. If a person is experiencing an active infection, the virus can be picked up by mosquitoes when they drink that person’s blood. The virus cannot survive outside of the body. Most human infections of ZIKV are transmitted by the Aedes mosquito, but the virus can also spread directly through sexual contact and blood transfusions.

Question 31

How does Zika pass through the placenta to reach the fetus?

Answer 31

ZIKV passes through the placenta by infecting placental cells. Placental macrophages (known as Hofbauer cells) and trophoblasts are the main target cells of ZIKV infection.

Question 32

What is the hypothesis for why ZIKV spread from Southeast Asia to the Americas after 2013?

Answer 32

A single substitution (Ser139 to Asn) in the viral polyprotein substantially increased ZIKV infection in model systems and caused more severe microcephaly and fetal death in mice. The S139N substitution arose sometime between November 2012 and October 2013 and has been stably maintained in the epidemic strains since.

Question 33

Radiation as a teratogen

Answer 33

Ionizing radiation can cause physical damage to the brains of developing fetuses at an 0.05- 0.5 Gy acute dose, during the period of 8-15 weeks post-conception. The effects include microcephaly and intellectual disabilities. The higher the dose, the lower the child’s IQ.

Question 34

Radiation as a mutagen

Answer 34

Ionizing radiation causes DNA mutations. X-rays cause large chromosomal abnormalities and smaller changes as well. One type of non-ionizing radiation, UV light, can cause mutations by linking neighboring pyrimidines covalently, which leads to the replacement of Cs with Ts during DNA replication.

Question 35

Radiation as a carcinogen

Answer 35

Any time random mutations are occurring, the risk for cancer increases above baseline. For example, melanoma is strongly linked to UV light exposure, which only penetrates the top layer of the skin.