Next: Cell Division and Cancer

CB 5.25

Genes are the parts of DNA that contain information.

Protein

For life to exist, the information (genes) must be passed on.

{Mitosis:producing more cells}

{Meiosis:producing gametes}

CB 13.5

Mitosis

Mitosis plays a role in:• Growth and Development

• Repair and Turnover of Cells

• Reproduction

–Asexual

The Cell Cycle

[DNA Replication]

CB 12.5

Complementary base pairs suggest how DNA replication may occur

CB 16.9

DNA replication: each strand serves as a template for making a complementary copy

O.R.

Origin of Replication

CB16.12b

O.R.

DNA replication: each strand serves as a template for making a complementary copy

CB16.12b

The two strands of DNA are unwound.

DNA replication: each strand serves as a template for making a complementary copy

CB16.12b

The DNA is copiedby DNA polymerase (a protein).

DNA replication: each strand serves as a template for making a complementary copy

CB16.12b

More unwinding, more copying

DNA replication: each strand serves as a template for making a complementary copy

CB16.12b

The DNA has now been copied. There are now two double-stranded DNAs

DNA replication: each strand serves as a template for making a complementary copy

CB16.12b

Most DNA has multiple origins of replication

CB16.12b

DNA replication:each strand serves as a template for producing a complementary copy

CB 5.28

Sometimes errors are made.

Luckily, errors can be repaired.

Error

DNA Repair

CB 16.18

Damage or replication error

Mismatch removed by enzymes

DNA replaced

Repair complete

Is recognized as NEW and mismatches are repaired

Not all errors get repaired.These are mutations.

3,000,000,000 (3 billion) base pairs/human cellwith1 error/1 billion base pairs not repaired= (average)~6 errors each time DNA is replicated

Errors are made during DNA replication

Only mutations in gametes will be passed on.

Mutations can be lethal, or can lead to cancer.

Cancer: Cell Division Gone Wrong

Cell division is regulated by bothpositive and negative signals.

Positive signals start the processof cell division.

Negative signals inhibit cell division.

CB 12.14

Normal Mammalian Cells Have Contact Inhibition

CB 12.19

Cancer Cells Do Not Have Contact Inhibition

CB 12.19

Cancer:

• is the loss of control over cell division.

• Tumors are normal cells that are dividing inappropriately.

– They stop performing their “normal” function, and are dividing repeatedly.

Tumors in a Livernormal

tumors

Cancer Cells

Normal Cells

A cell becomes cancerous when there are incorrect positive AND negative

signals.

Multiple mutations are required for a single cell to become cancerous.

CB18.22

GO! STOP!

cancer

CB18.21

Multiple mutations are required for a single cell to become cancerous.

CB18.22

Benign versus Malignant cancer CB12.20

Image from: www.utm.utoronto.ca/~w3bio315/lecture22.htm

How do these mutations arise?

CB18.22

Causes of mutations:

• Replication errors– Exacerbated by poor DNA repair

• Genetic predispositions for poor repair or already having some mutations

Causes of mutations:

• Replication errors– Exacerbated by poor DNA repair

• Other biological agents– Viruses– Transposons

Causes of mutations:

• Replication errors– Exacerbated by poor DNA repair

• Other biological agents– Viruses– Transposons

• Environmental factors– Ultraviolet light– Mutagenic chemicals

• smoking, industrial waste, natural toxins

Environment plays a large role in the chance of contracting cancer…

The multiethnic cohort study: exploring genes, lifestyle and cancer risk. L Kolonel, D Altshuler, B Henderson (July 2004) Nature Reviews Cancer 4, 519-527 Fig 1

Causes of mutations:

• Replication errors– Exacerbated by poor DNA repair

• Other biological agents– Viruses– Transposons

• Environmental factors– Ultraviolet light– Mutagenic chemicals

• smoking, industrial waste, natural toxins

Source: Centers for Disease Control and Prevention: http://www.cdc.gov/nchs/fastats/deaths.htm.

U.S. Mortality, 2007Rank Cause # deaths %

1. Heart disease 616,067 33.4

2. Cancer 562,875 30.5

3. Stroke 135,952 7.4

4. Respiratory diseases 127,924 6.9

5. Accidents 123,706 6.7

6. Alzheimer's disease 74,632 4.0

7. Diabetes 71,382 3.9

8. Influenza and Pneumonia 52,717 2.9

9. Kidney disease 46,448 2.5

10. Septicemia 34,828 1.9

Change in the US Death Rates* by Cause, 1950 & 2000

* Age-adjusted to the 2000 US standard population.Source: US Mortality Volume 1950, National Vital Statistics Report, 2002, Vol. 50, No. 15.

586.8

180.5

48.160.923.7

200.9193.7

258.2

0

100

200

300

400

500

600

HeartDiseases

Stroke Pneumonia/Influenza

Cancer

1950

2000

Rate Per 100,000

Cancer Death Rates*, for Men, US, 1930-1999

*Age-adjusted to the 2000 US standard population.Source: US Mortality Public Use Data Tapes 1960-1999, US Mortality Volumes 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2002.

0

20

40

60

80

100

1930 1935 1940 1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995

Lung

Colon and rectum

Prostate

Pancreas

Stomach

Liver

Rate Per 100,000

Leukemia

Cancer Death Rates*, for Women, US, 1930-1999

*Age-adjusted to the 2000 US standard population.Source: US Mortality Public Use Data Tapes 1960-1999, US Mortality Volumes 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2002.

0

20

40

60

80

100

1930 1935 1940 1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995

Lung

Colon and rectum

Uterus

Stomach

Breast

Ovary

Pancreas

Rate Per 100,000

Tobacco Use in the US, 1900-1999

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

190019051910191519201925193019351940194519501955196019651970197519801985199019952000Year

Per Capita Cigarette Consumption

0

10

20

30

40

50

60

70

80

90

100

Age-Adjusted Lung Cancer Death

Rates*

*Age-adjusted to 2000 US standard population.

Source: Death rates: US Mortality Public Use Tapes, 1960-1999, US Mortality Volumes, 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2001. Cigarette consumption: Us Department of Agriculture, 1900-1999.

Per capita cigarette consumption

Male lung cancer death rate

Female lung cancer death rate

Tobacco Use in the US, 1900-1999

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

190019051910191519201925193019351940194519501955196019651970197519801985199019952000Year

Per Capita Cigarette Consumption

0

10

20

30

40

50

60

70

80

90

100

Age-Adjusted Lung Cancer Death

Rates*

*Age-adjusted to 2000 US standard population.

Source: Death rates: US Mortality Public Use Tapes, 1960-1999, US Mortality Volumes, 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2001. Cigarette consumption: Us Department of Agriculture, 1900-1999.

Per capita cigarette consumption

Male lung cancer death rate

Female lung cancer death rate

Next:In class exercise- Funding cancer researchand How can mutations be minimized?