Mechanisms of Carcinogenesis & Effects of Embryo and Fetus

it damages DNA by changing a specific gene

How does a carcinogen cause cancer?

-initiation

-promotion

-progression

What are the three stages of a carcinogen causing cancer?

-permanently changed but does not cause cancer, unless exposed to threshold level

-is transformed and produces cancer cell line if the initiator is a complete carcinogen (like cig smoke, asbestos, alcohol)

When a carcinogen damages DNA, what are the two possible ways the DNA is affected?

False, there is time between the initiating even and clinical appearance of a tumor which may be years or decades

T/F: Carcinogens produces an immediate cancer

initiation

During the ________ phase of carcinogenesis, the cell appears somewhat normal and still functions normally, this cell may be referred to as dysplastic or premalignant

promotion

During the _____________ phase of carcinogenesis, the altered cells proliferate and involves an agent that encourages or enhances cell growth

False

T/F: A promoting agent acts directly on DNA to induce tumor growth

threshold

Promoting factors have a ____________ level

initiating factor

Promoting factors will not cause tumor growth when applied before _______________

other parts of the cell

Promoting agents do not act directly on DNA, so what does it react with?

Yes, they may be reversible if periods between exposure are prolonged

Are effects of promoters reversible?

progression

What mechanism of carcinogenesis involves invasion, cells are dividing which increases the bulk of the tumor, it can locally spread or metastasize?

metastasis

_____________ involves local invasion, detachment and embolization, and arrest in distant organ capillary beds, and extravasation

angiogenesis

________________ happens at the primary tumor site for metastasis

-proto oncogenes

-oncogenes

-anti oncogenes

What are the three genes involved in the tumor process?

proto-oncogenes

What kind of gene is considered a "normal gene", and controls normal growth and differentiation?

oncogenes

What kind of gene contributes to abnormal proliferation of cells through point mutations, translocations, and gene amplification

anti-oncogenes

What kind of gene is also called a "tumor suppressor gene", and the inactivation allows the malignant process to thrive?

False, not been able to identify a dose and many cases lack data

T/F: We have been able to identify a dose to give carcinogenesis a threshold dose due to many variables and in many cases have good data

animals

It is important to see the dose response curve, so we study it on ____________

-incidence increases with increase dose, BUT to a certain point

-after that point the curve decreases due to cell death

A dose response curve tells us two things... what are they?

latent period

_________ is the time interval between irradiation and the appearance of malignancy

leukemia

_________________ has the shortest latent period, from atomic bomb survivor data, 7-12 years

solid tumor

____________ have a latent period of 10-50 years, which suggest that data should look at age of expression and NOT age of induction

True

T/F: Data has been mixed about secondary malignancies in radiation therapy patients

True

T/F: Small studies or one institution studies have found secondary malignancies to be low and not significant

1. a sufficiently large number of patients

2. a suitable comparison group (patients with the same cancer)

3. a sufficiently long follow up for radiation induced solid tumors to become malignant

For data on secondary malignancies to be creditable, the study must be:

True

T/F: Whenever large studies have been available they show statistically significant data, very low numbers, but enough for secondary malignancies should always be a concern and chronic side effects

fertilization through week 13

What time is the first trimester?

14 through 27 weeks

What time is the second trimester?

28 weeks through 41 weeks

What time is the third trimester?

blastocyst

In the first trimester, it starts with fertilization and at 3 weeks the ____________ has implanted

embryo

In the first trimester at 4 weeks, they are now called an ___________

10

During pregnancy, at week _____ all organs have formed and continue to develop

second

During the ___________ trimester the baby can...

- hear, taste, and move

- react to noise and movement

- practice breathing

- open and close their eyes

third

During the _________ trimester the baby...

- starts to put on fat

- nails and hair start to grow

- billions of neurons are added to their brain

- lungs get ready to take first real breath

developmental

With pregnancy, development of cancer is always a concern but also ______________ effects

- lethal

- malformations

- growth disturbances

What are the three developmental effects of RT during pregnancy?

prenatal death

Death before birth

neonatal death

Death at birth

lethal

Which developmental effect?

- before or immediately after implantation of embryo in uterine wall (before week 4)

- increased higher dose during all stages of development

- both cause death

malformations

Which developmental effect?

- exposure during major organogenesis in which main body structures are formed (week 5)

Growth disturbances

Which developmental effect?

- can happen at all stages of development but occurs most often at later stages of pregnancy

- dose

- stage of pregnancy

- dose rate

What are some important factors to consider with pregnancy and RT developmental effects?

- preimplantation

- organogenesis

- fetal stage

What are the three stages of pregnancy?

preimplantation

Which stage of pregnancy?

- day 1-34 or roughly 4 weeks

- most sensitive stage (RT lethal)

- all or nothing = embryo either doesn't implant and dies or implants and grows and develops

preimplantation

What is the most sensitive stage of pregnancy?

organogenesis

What stage of pregnancy?

- day 35-42 or week 5

- sensitive to a variety of congenital abnormalities

- if death is to occur it's usually neonatal

neonatal

If death is to occur during the organogenesis stage of pregnancy, it is typically __________

congenital abnormalities

Examples include, organs developing outside of the body, growth retardation, facial abnormalities

fetal

Which stage of pregnancy?

- day 42 to birth, week 6

- more damage at earlier part of fetal phase

- documented effects on hematopoietic system, liver, and kidney

- gonads both morphologically and function in both genders

- growth retardation

- atomic bomb survivors

- medical exposures

Where did we get data from on radiation exposure during pregnancy?

1

Before 18 weeks, a dose of ___ Gy will kill 50% of embryos

5

Before 18 weeks, a dose of ____ Gy will kill 100% of embryos

- microcephaly

- CNS defects

- growth retardation

What are the most common abnormalities of radiation exposure during pregnancy?

controversial

Studies about cancer incidence in children irradiated in utero are considered ________________ due to children being inflicted with cancer and assuming that an x-ray mom had while they were in utero was the cause-hard is to be determined

last

Fetus exposed to low-dose irradiation in ______ trimester have increased risk of childhood malignancies

40%

An obstetric x-ray exam results in a ____% increase risk of childhood cancer over the spontaneous level

10

Radiation doses of ____ mGy increases the risk of childhood cancers when irradiated in utero

gestation

Exposure of fetus for entire ___________ period is 5 mSV or 0.5 rem

monthly

Occupational exposure of women has a __________ exposure not exceeding 0.5 mSv or 0.05 rem

safety officer

Once an occupational worker declares herself pregnant, her duties should be reviewed with the radiation ________ ________