The Cell Cycle & Cancer Questions we will try to answer 1. What is cancer? 2. How are cancerous cells different than normal cells? 3. How do you get cancer? i.e. What makes normal cells become cancer cells?

What is cancer? Cancer is … Cancer cells cannot stop dividing Cell cycle

Fig 8.7

The Events of the Interphase Divided into 3 phases: G1 – S – G2 –

Length of G1 can vary greatly:

Cell Division or “M” phase Cell Division consists of two parts 1. Mitosis: 2. Cytokinesis: What needs to happen to the chromosomes prior to Mitosis? During mitosis?

Fig 8.6

Sketch of one duplicated chromosome Each chromatid has one DNA molecule Sister chromatids How do sister chromatids compare genetically? What happens to sister chromatids during mitosis? Centromere

S-Phase: DNA Replication Mitosis: sister chromatids separate Two-chromatid chromosome One-chromatid chromosome One-chromatid chromosome S-Phase: DNA Replication Interphase

Mitosis: Division of the Nucleus Four Stages: Prophase – Metaphase – Anaphase –centromeres break and the chromosomes (now single chromatids) migrate to opposite poles Telophase – nuclear envelope forms around each cluster of chromosomes

Fig 8.8

Cytokinesis: division of the cytoplasm to create 2 new cells

Fig 8.9

Produces somatic (body) cells Mitosis Produces somatic (body) cells Meiosis produces gametes Fig 8.14

Normal Karyotype of Human Chromosomes How many pairs of chromosomes in this Karyotype? Paired chromosomes are homologous How do you inherit chromosomes? What gender? Sex vs. autosomal chromosomes?

Sex chromosomes determine a person’s gender Humans have 46 chromosomes: Sex chromosomes:

Diploid cell: 6 total chromosomes, 3 sets of homologous chromosomes Haploid cell Haploid cell One set of non-homologous chromosomes One set of non-homologous chromosomes

Regulation of Cell Division What evidence in your own life do you have that cell division is regulated by your body? What normally controls cell division?

Contact Inhibition Cells do not normally grow or divide when in contact w/ other cells

Contact inhibition does not occur in Cancerous Cells Cancerous cells continue growing and moving when they touch other cells.

Fig 8.10

Cell cycle control

Growth factor binds to receptor Growth control in a normal cell Signaling cell Growth factor = Growth factor binds to receptor Receptor sets off a signal cascade to nucleus target cell enters S-phase and divides, eventually repairing wound target cell Nucleus

Several ways to get faulty growth control in a cancer cell 2. Mutant receptor might turn on even without binding growth factor Signal cascade might occur even without trigger from receptor 1. Cell might produce its own growth factor

The genetic basis of cancer (p.224-227 in Ch 11) Proto-oncogenes: Oncogenes: genes that cause cancer Oncogenes are rarely inherited.....Why?

Tumor Suppressor Genes One mutant Tumor Suppressor Gene does not cause cancer....Why?

Fig. 11.20

BRCA 1: Breast Cancer Susceptibility Gene BRCA 1 is …. If a women inherits a mutant BRCA 1 she has a 80 to 90% chance of developing breast cancer Why aren’t the percentages 100%? Why are the percentages (10%) much lower for the average woman?

Environmental causes of cancer Viruses Chemicals Radiation **All can cause mutations in tumor-suppressor genes and proto-oncogenes

Characteristics of all cancer cells Immortal Altered cell membranes Have lost the genetic ability to stop dividing Cancer is heritable: Are dedifferentiated No contact inhibition If not treated will eventually cause death

Cancer treatment: Attack Actively Dividing Cells Three treatments for cancer: Surgery Radiation Phase-specific chemotherapies

Phase-specific Chemotherapies Prevent cells from entering the S-phase Block the S phase Block or stop mitosis

But chemotherapy can’t discriminate between cancer cells and normal cells…. May affect all rapidly dividing cells Which cells divide rapidly? So.... what would be the side effects?

Side Effects of Chemotherapy

How to lower your Cancer Risks Eat plenty of fiber Fiber speeds passage through digestive tract Do not smoke Drink alcohol in moderation or not at all Exercise regularly Do not become overweight Limit dietary fat Limit sun exposure or use sunscreen Learn to recognize the warning signs of cancer

Common Warning Signs of Cancer: C.A.U.T.I.O.N. C - change in bowel or bladder habits A - a sore that does not heal U - unusual bleeding or discharge T - thickening or lump in the breast or any part of the body I - indigestion or difficulty swallowing O - obvious change in a wart or mole N - nagging cough or hoarseness

Down Syndrome - Incidence with Mother’s age 1 in 1000 births in U.S. 1 in 12 births for moms that are 50 years old Most frequent genetic cause of mental retardation I.Q. = 20-50

Down Syndrome as function of mother’s age – Fig 8.23

Human Somatic Cells have 46 Chromosomes How many chromosomes in human gametes?

Down Syndrome Meiosis

Down Syndrome Karyotype What is wrong with the Karyotype? Why are most trisomies fatal? (except sex chromo’s)

What if gametes were made by mitosis? Human Life Cycle Meiosis What if gametes were made by mitosis? Fig 8.14

Fig 8.15

Fig 8.16 Meiosis I

Stages of Meoisis Interphase – Meiosis I Prophase I – Metaphase I – Anaphase I – Telophase I – Meiosis II Prophase II – chromosomes attach to spindle Metaphase II – chromosomes align at equator Anaphase II – sister chromatids separate Telophase II – cells divide, end result = 4 haploid daughter cells

Normal Meiosis Interphase diploid 2n How do the chromo’s align at metaphase I? What separates at anaphase I? How do the chromo’s align at metaphase II? What separates at anaphase II? n n Meiosis I Meiosis II n n n n

Fig 8.17

Normal Meiosis followed by Fertilization Meiosis I Meiosis II Product of meiosis Fertilization Zygote Normal sperm Chromosomes: Both daughter cells have one copy of each chromosome Normal diploid zygote

Genetic Basis of Down Syndrome: Nondisjunction: in Meiosis I: Or In Meiosis II:

Fig 8.20

Age of Mom vs. Age of Dad Why is the age of the mother, but not the father, correlated with the probability of having a child with Down Syndrome?

Egg formation in humans Pre-egg cells present before girls are born -- about 1000 or so. Pre-egg cells are stuck at metaphase I Ovulation:

Mom’s Pre-egg Cells form Prenatally Half of you was present inside your grandmother as a single cell inside your mom when she was a fetus. At about 12 years, women start ovulating one egg each month for next 40 years. So …..A 50 yr old woman has had her eggs sitting with chromosomes aligned in metaphase for over 50 years! Nondisjunction is rarely seen with chromosomes larger than #20--Why? .

Why doesn’t the age of the father influence the rate of Down syndrome? Sex cell formation in Males:

Genetic Screening for Down Syndrome Can we detect D.S. before birth? Amniocentesis: fetus located using ultrasound, needle inserted and amniotic fluid extracted Fluid contains fetal urine and fetal cells from skin, respiratory tract, urinary tract Make karyotype to detect abnormal chromosome numbers. Not performed until 16th week of pregnancy

Chorionic Villus Sampling (CVS) Catheter inserted vaginally and chorionic tissue removed 9-11 weeks after conception results of tests within days rather than weeks as in amniocentesis But may be slightly riskier for fetus

Meiosis Causes Genetic Variation 1. Independent Assortment = Thus maternal and paternal chromosomes are shuffled 223 or 8,388,608 different possibilities from each parent, then fertilization gives 70 trillion

Fig. 8.18

2nd Reason for Genetic Variation 2. Crossing over Result:

Fig 8.19